bims-kimdis 2022-12-11 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2022–12–11
25 papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins

Does the ketogenic ratio matter when using ketogenic diet therapy in pediatric epilepsy?
Ketone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma.
The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review.
Clinical Assessment of Intermittent Fasting With Ketogenic Diet in Glycemic Control and Weight Reduction in Patients With Type II Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Assessing the Feasibility of Using the Ketogenic Diet in Autism Spectrum Disorder.
The Efficacy of the Ketogenic Diet in Improving Seizures and EEG Findings in Patients with Refractory Infantile Spasms.
Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels.
Ketogenic-Diet Shake Containing Uncaria tomentosa-Associated Acute Interstitial Nephritis.
Sodium butyrate administration modulates the ruminal villus height, inflammation-related gene expression, and plasma hormones concentration in dry cows fed a high-fiber diet.
Modeling digestion, absorption, and ketogenesis after administration of tricaprilin formulations to humans.
Euglycemic diabetic ketoacidosis and COVID-19 management in a term pregnant patient; a case report.
Inflammation level in type 2 diabetes is associated with dietary advanced glycation end products, Mediterranean diet adherence and oxidative balance score: A pathway analysis.
Inflamed adipose tissue: A culprit underlying obesity and heart failure with preserved ejection fraction.
The bidirectional relationship between AMPK pathway activation and myokine secretion in skeletal muscle: How it affects energy metabolism.
Effects of dietary energy density and feeding strategy during the dry period on feed intake, energy balance, milk production, and blood metabolites of Holstein cows.
Editorial: Muscle mass and function in COVID-19.
Insufficient sleep predicts poor weight loss maintenance after one year.
The attack of the clones to the cardiovascular system.
Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84.
The association between gut hormones and diet-induced metabolic flexibility in metabolically healthy adults.
Dietary supplements for lipedema.
Role of physical activity and cardiorespiratory fitness in metabolically healthy obesity: a narrative review.
SGLT-2 Inhibitor Prescribing Practices.
Physical exercise, inflammation, and hypertension: how to improve cardiovascular prevention.
Dietary restriction in senolysis and prevention and treatment of disease.

Epilepsia. 2022 Dec 05.

Does the ketogenic ratio matter when using ketogenic diet therapy in pediatric epilepsy?

Suvasini Sharma, Robyn Whitney, Eric H Kossoff, Rajesh RamachandranNair.

  The ketogenic diet (KD) is a widely used therapeutic option for individuals with medically refractory epilepsy. As the diet's name implies, ketosis is a historically important component of the diet, but it is not well understood how important ketosis is for seizure control. The ketogenic ratio is defined as the ratio of fat to carbohydrate plus protein by weight in the diet (grams). Traditionally, the classic KD contains a 4:1 ratio, and a very high proportion of fat in the diet. The classic KD, with its high proportion of fat and limited carbohydrate intake can be restrictive for patients with epilepsy. Recently, there is experience with use of lower ketogenic ratios and less restrictive diets such as the modified Atkins diet and the low glycemic index treatment. In this narrative review, we examine the role of ketosis and ketogenic ratios in determining the efficacy of the ketogenic diet in children with epilepsy.

Keywords:  Drug resistant epilepsy; beta hydroxybutyrate; ketone bodies; low glycemic index treatment; low ratio diets; modified Atkins diet

DOI:  https://doi.org/10.1111/epi.17476
J Allergy Clin Immunol Glob. 2022 Nov;1(4): 282-298

Ketone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma.

Madeleine M Mank, Leah F Reed, V Amanda Fastiggi, Paola E Peña-García, Laura R Hoyt, Katherine E Van Der Vliet, Jennifer L Ather, Matthew E Poynter.

   Background: Individuals with allergic asthma exhibit lung inflammation and remodeling accompanied by methacholine hyperresponsiveness manifesting in proximal airway narrowing and distal lung tissue collapsibility, and they can present with a range of mild-to-severe disease amenable or resistant to therapeutic intervention, respectively. There remains a need for alternatives or complements to existing treatments that could control the physiologic manifestations of allergic asthma.
Objectives: Our aim was to examine the hypothesis that because ketone bodies elicit anti-inflammatory activity and are effective in mitigating the methacholine hyperresponsiveness associated with obese asthma, increasing systemic concentrations of ketone bodies would diminish pathologic outcomes in asthma-relevant cell types and in mouse models of allergic asthma.
Methods: We explored the effects of ketone bodies on allergic asthma-relevant cell types (macrophages, airway epithelial cells, CD4 T cells, and bronchial smooth muscle cells) in vitro as well as in vivo by using preclinical models representative of several endotypes of allergic asthma to determine whether promotion of ketosis through feeding a ketogenic diet or providing a ketone precursor or a ketone ester dietary supplement could affect immune and inflammatory parameters as well as methacholine hyperresponsiveness.
Results: In a dose-dependent manner, the ketone bodies acetoacetate and β-hydroxybutyrate (BHB) decreased proinflammatory cytokine secretion from mouse macrophages and airway epithelial cells, decreased house dust mite (HDM) extract-induced IL-8 secretion from human airway epithelial cells, and decreased cytokine production from polyclonally and HDM-activated T cells. Feeding a ketogenic diet, providing a ketone body precursor, or supplementing the diet with a ketone ester increased serum BHB concentrations and decreased methacholine hyperresponsiveness in several acute HDM sensitization and challenge models of allergic asthma. A ketogenic diet or ketone ester supplementation decreased methacholine hyperresponsiveness in an HDM rechallenge model of chronic allergic asthma. Ketone ester supplementation synergized with corticosteroid treatment to decrease methacholine hyperresponsiveness in an HDM-driven model of mixed-granulocytic severe asthma. HDM-induced morphologic changes in bronchial smooth muscle cells were inhibited in a dose-dependent manner by BHB, as was HDM protease activity.
Conclusions: Increasing systemic BHB concentrations through dietary interventions could provide symptom relief for several endotypes of allergic asthmatic individuals through effects on multiple asthma-relevant cells.

Keywords:  Asthma; ketogenic diet; ketones; methacholine; mice

DOI:  https://doi.org/10.1016/j.jacig.2022.08.001
J Psychiatr Brain Sci. 2022 ;pii: e220009. [Epub ahead of print]7(5):

The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review.

Shebani Sethi, Judith M Ford.

  In search of interventions targeting brain dysfunction and underlying cognitive impairment in schizophrenia, we look at the brain and beyond to the potential role of dysfunctional systemic metabolism on neural network instability and insulin resistance in serious mental illness. We note that disrupted insulin and cerebral glucose metabolism are seen even in medication-naïve first-episode schizophrenia, suggesting that people with schizophrenia are at risk for Type 2 diabetes and cardiovascular disease, resulting in a shortened life span. Although glucose is the brain's default fuel, ketones are a more efficient fuel for the brain. We highlight evidence that a ketogenic diet can improve both the metabolic and neural stability profiles. Specifically, a ketogenic diet improves mitochondrial metabolism, neurotransmitter function, oxidative stress/inflammation, while also increasing neural network stability and cognitive function. To reverse the neurodegenerative process, increasing the brain's access to ketone bodies may be needed. We describe evidence that metabolic, neuroprotective, and neurochemical benefits of a ketogenic diet potentially provide symptomatic relief to people with schizophrenia while also improving their cardiovascular or metabolic health. We review evidence for KD side effects and note that although high in fat it improves various cardiovascular and metabolic risk markers in overweight/obese individuals. We conclude by calling for controlled clinical trials to confirm or refute the findings from anecdotal and case reports to address the potential beneficial effects of the ketogenic diet in people with serious mental illness.

Keywords:  bipolar disorder; functional connectivity; insulin resistance; metabolic psychiatry; metabolism; neural network stability; psychotic symptoms; schizophrenia

DOI:  https://doi.org/10.20900/jpbs.20220009
Cureus. 2022 Oct;14(10): e30879

Clinical Assessment of Intermittent Fasting With Ketogenic Diet in Glycemic Control and Weight Reduction in Patients With Type II Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Hany A Zaki, Haris Iftikhar, Abeer Abdalrubb, Nood Dhafi R Al-Marri, Mohammed Gafar Abdelrahim, Mohamed Fayed, Mohamed Abdelgadir M Elgassim, Mohamed A Elarref.

  Diabetes mellitus (DM) is a global epidemic causing significant morbidity and mortality. The most occurring DM is type 2 diabetes mellitus (T2DM) which has similar symptoms as type 1 diabetes mellitus (T1DM). However, it is less marked, making it difficult to diagnose during the early stages. The management of T2DM is usually based on weight and glycemic control, which can be achieved through dietary interventions such as intermittent fasting (IF) and the ketogenic diet (KD). Therefore, this systematic review and meta-analysis aim to demonstrate the role of IF and KD in glycemic and weight control among patients with T2DM. Two methods, including an electronic database search through ScienceDirect, Google Scholar, PubMed, Scopus, Embase, and Web of Science, and a manual search were used to identify relevant studies published between 2000 and 2022. The search yielded 1299 articles, of which only 12 met the inclusion criteria. In addition, study quality appraisal was performed using Review Manager software (RevMan 5.4.1). The pooled results have shown that IF had a similar effect on HBA1c reduction as control interventions (standardized mean differences [SMD]: 0.36%; 95% CI; -0.37, 1.10; P = 0.33, I2 = 87%). Similarly, an insignificant difference in weight reduction between IF and control interventions was recorded (SMD: -1.05%; 95% CI; -2.29, 0.19; P = 0.10, I2 = 96%). On the other hand, KD significantly reduced body weight compared with control diets (SMD: -1.91 kg; 95% CI; -2.96 kg, -0.85 kg; P = 0.0004, I2 = 96%). Similarly, KD had a better effect on the HBA1c percentage reduction than control diets (SMD: -2.00%; 95% CI; -3.76, -0.25; P = 0.03, I2 = 97%). IF and KD have shown reductions in HBA1c and body weight among patients with T2DM. However, the interventions are subject to side effects and should be used with caution and under the supervision of a health professional.

Keywords:  diabetes mellitus type 2; glycated hemoglobin (hba1c); glycemic control; intermittent energy restriction; intermittent fasting; ketogenic; time-restricted fasting; very low-carbohydrate diet

DOI:  https://doi.org/10.7759/cureus.30879
J Hum Nutr Diet. 2022 Dec 07.

Assessing the Feasibility of Using the Ketogenic Diet in Autism Spectrum Disorder.

Jacob Albers, Gearta Kraja, Danielle Eller, Karen Eck, Danielle McBrian, Jennifer M Bain.

  Evidence demonstrating efficacy of dietary interventions for autism spectrum disorder (ASD) remains inconsistent. Recent research on the ketogenic diet (KD) for the treatment of ASD has suggested benefit. Children with ASD often demonstrate ritualized food specific behaviors, taste and texture aversions, and an increased prevalence of food restrictions and allergies. There is a need to investigate how these features contribute to initiation and adherence of the KD. Two surveys were administered to assess the feasibility of utilizing the KD for ASD. First, paper surveys were given to caregivers of children presenting to outpatient neurology clinics. Next, experienced clinicians were recruited and surveyed online using Redcap. χ2 analysis was used to compare ASD and non ASD caregiver responses. Descriptive metrics were used to present clinician responses. Responses to each question were evaluated individually. This article is protected by copyright. All rights reserved.

Keywords:  Autism; Ketogenic Diet

DOI:  https://doi.org/10.1111/jhn.13115
Iran J Child Neurol. 2022 ;16(4): 45-54

The Efficacy of the Ketogenic Diet in Improving Seizures and EEG Findings in Patients with Refractory Infantile Spasms.

Melika Hanifiha, Reza Shervin Badv, Maryam Mahmoudi, Ali Reza Tavasoli.

   Objectives: Infantile spasm is an epileptic disorder of early childhood and infancy and is characterized by cluster epileptic spasms and abnormal EEG findings. Developmental delay is prevalent. Some studies have indicated the significant effect of the Ketogenic Diet (KD) on intractable spasms in children who are unresponsive to first-line treatments. It has been used successfully as a first-line treatment with fewer side effects than ACTH.
Materials & Methods: This was an interventional study in which the effectiveness of KD over a six-month period was evaluated in patients with infantile spasms. Those who fulfilled the inclusion criteria and were willing to use the diet received free cans of the 4:1 ketogenic formula. The diet was prescribed based on the Johns Hopkins protocol in the outpatient setting. All patients used a full formula diet for one month. After a month, the patients were examined by a neurologist and a dietitian, and an EEG was obtained to compare pre- and post-KD findings. In order to compare pre- and post-KD seizures, the maximum number of seizures was multiplied by the longest duration of seizures.
Results: Ten patients were assessed for one month. Using the KD led to significant changes in seizures/clusters and EEG findings. Nine parents reported improvement in their children's social interactions after using the KD.
Conclusion: Based on the findings of this study, the KD can control seizures in patients suffering from infantile spasms by reducing seizure frequency & duration and improving EEG findings.

Keywords:  infantile spasm; ketogenic diet; refractory seizure

DOI:  https://doi.org/10.22037/ijcn.v16i3.31429
Orphanet J Rare Dis. 2022 Dec 05. 17(1): 423

Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels.

Emily Shelkowitz, Russell P Saneto, Walla Al-Hertani, Charlotte M A Lubout, Nicholas V Stence, Mark S Brown, Patrick Long, Diana Walleigh, Julie A Nelson, Francisco E Perez, Dennis W W Shaw, Emma J Michl, Johan L K Van Hove.

   BACKGROUND: Nonketotic hyperglycinemia (NKH) is a severe neurometabolic disorder characterized by increased glycine levels. Current glycine reduction therapy uses high doses of sodium benzoate. The ketogenic diet (KD) may represent an alternative method of glycine reduction.
AIM: We aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate.
METHODS: Six infants with NKH were first treated with high dose benzoate therapy to achieve target plasma glycine levels, and then switched to KD with low dose benzoate. They were evaluated as clinically indicated by physical examination, electroencephalogram, plasma and cerebral spinal fluid amino acid levels. Brain glycine levels were monitored by magnetic resonance spectroscopy (MRS).
RESULTS: Average plasma glycine levels were significantly lower with KD compared to benzoate monotherapy by on average 28%. Two infants underwent comparative assessments of brain glycine levels via serial MRS. A 30% reduction of brain glycine levels was observed in the basal ganglia and a 50% reduction in the white matter, which remained elevated above normal, and was equivalent between the KD and high dose benzoate therapies. CSF analysis obtained while participants remained on the KD showed a decrease in glycine, serine and threonine levels, reflecting their gluconeogenetic usage. Clinically, half the patients had seizure reduction on KD, otherwise the clinical impact was variable.
CONCLUSION: KD is an effective glycine reduction method in NKH, and may provide a more consistent reduction in plasma glycine levels than high-dose benzoate therapy. Both high-dose benzoate therapy and KD equally reduced but did not normalize brain glycine levels even in the setting of low-normal plasma glycine.

Keywords:  Benzoate; Epilepsy; Glycine; Ketogenic diet; Magnetic resonance spectroscopy; Nonketotic hyperglycinemia

DOI:  https://doi.org/10.1186/s13023-022-02581-6
Case Rep Nephrol Dial. 2022 Sep-Dec;12(3):12(3): 219-225

Ketogenic-Diet Shake Containing Uncaria tomentosa-Associated Acute Interstitial Nephritis.

Gilda Portalatin, Shruti Shettigar, Astrid Carrion-Rodriguez, Sushma Medikayala, Leal Herlitz, Dianne Sandy, Surafel K Gebreselassie, Shane A Bobart.

  Uncaria tomentosa is a plant that has been used in traditional medicine for its anti-inflammatory, immunomodulatory, and immunostimulant properties. As a result, it can be found in several over-the-counter supplements worldwide. Acute interstitial nephritis (AIN) can be due to an offending medication, infection, or autoimmunity. We present a case of a patient who was on a strict ketogenic diet, utilizing over-the-counter diet shakes containing the herbal supplement Uncaria tomentosa who developed acute kidney injury with a serum creatinine of 3.6 mg/dL up from a baseline of 0.7 mg/dL. Serological evaluation was negative, and kidney biopsy revealed interstitial inflammatory infiltrates including focally prominent eosinophils and multifocal tubulitis. Stopping the keto-diet shake containing Uncaria tomentosa and concomitant corticosteroid therapy resulted in improvement in kidney function to near baseline. To our knowledge, this is the only biopsy-proven case of AIN in the setting of Uncaria tomentosa use.

Keywords:  Acute interstitial nephritis; Keto shake; Keto-diet; Kidney biopsy

DOI:  https://doi.org/10.1159/000526391
Anim Sci J. 2022 Jan;93(1): e13791

Sodium butyrate administration modulates the ruminal villus height, inflammation-related gene expression, and plasma hormones concentration in dry cows fed a high-fiber diet.

Rika Fukumori, Kazuya Doi, Taisei Mochizuki, Shin Oikawa, Satoshi Gondaira, Tomohito Iwasaki, Kenichi Izumi.

  The objectives of this study were to evaluate the effects of sodium butyrate on the ruminal villus morphology, mRNA expression associated with nutrient metabolism and inflammation in the ruminal epithelium, and plasma concentrations of metabolites and hormones in non-lactating cows fed a high-fiber diet. Four Holstein cows with a rumen cannula were assigned to two treatments in a crossover design. The treatments were ruminal administration of sodium butyrate premix or control premix before feeding to cows fed the same total mixed ration mainly composed of glass silage once a day. Sodium butyrate was provided at a butyrate dose of 0.04% per kg body weight. The control premix was made by replacing sodium-butyrate with wheat bran. The plasma β-hydroxybutyrate concentration increased 3 to 6 h after the butyrate premix administration but returned to a concentration similar to that of the control before feeding. After continuous administration, increases in the ruminal villus height and plasma concentration of glucagon-like peptide-2, and lower gene expression of TNF-α, IL-1β, and TLR-2 in the rumen epithelium were observed in cows supplied with the butyrate premix. These results showed that sodium butyrate affects rumen epithelial morphology and plasma concentrations of hormones even under a low fermentable diet.

Keywords:  GLP-2; butyrate; dairy cow; inflammation-related gene; rumen papillae

DOI:  https://doi.org/10.1111/asj.13791
Eur J Pharm Biopharm. 2022 Dec 02. pii: S0939-6411(22)00281-8. [Epub ahead of print]

Modeling digestion, absorption, and ketogenesis after administration of tricaprilin formulations to humans.

Zhuoxuan Li, Gisela Ramirez, Rushi Tang, Cheong Kin Xian Paul, Murali Nair, Samuel Henderson, Bruce Morimoto, Julie Liu, Thomas Kaasgaard, Benjamin Boyd, Matthias G Wacker.

  At present, tricaprilin is used as a ketogenic source for the management of mild to moderate Alzheimer's disease. After administration of the medium-chain triglyceride, tricaprilin is hydrolyzed to octanoic acid and further metabolized to ketones, acting as an alternative energy substrate for the brain. In this investigation, we developed a physiologically based biopharmaceutics model simulating in vivo processes following the peroral administration of tricaprilin. The model includes multiple data sources to establish a partially verified framework for the simulation of plasma profiles. The input parameters were identified based on existing literature data and in vitro digestion studies. Model validation was conducted using the outcome of a phase I clinical trial. A partial parameter sensitivity analysis elucidated various influences on the plasma ketone levels that are mainly responsible for the therapeutic effects of tricaprilin. Based on our findings, we concluded that dispersibility and lipolysis of tricaprilin together with the gastric emptying patterns are limiting ketogenesis, while other steps such as the conversion of octanoic acid to ketone bodies play a minor role only.

Keywords:  Alzheimer’s disease; in vitro lipid digestion; ketogenesis; medium-chain triglycerides MCTs; physiologically based pharmacokinetic (PBPK) modeling; tricaprilin

DOI:  https://doi.org/10.1016/j.ejpb.2022.11.022
Clin Case Rep. 2022 Dec;10(12): e6705

Euglycemic diabetic ketoacidosis and COVID-19 management in a term pregnant patient; a case report.

Fatemeh Mohammadzade, Behnaz Khodabakhshi, Elahe Amiri, Amir Bigdeli, Fahimeh Abdollahi, Alireza Fatemi.

  In this case report, we report a Covid-19 infected female patient with gestational diabetes mellitus with primary manifestation of ketoacidosis at term pregnancy and discuss the management challenges with euglycemia and a high ketone burden.

Keywords:  COVID‐19; euglycemic; gestational diabetes; ketoacidosis; pregnancy

DOI:  https://doi.org/10.1002/ccr3.6705
J Diabetes Complications. 2022 Nov 13. pii: S1056-8727(22)00266-5. [Epub ahead of print]37(1): 108354

Inflammation level in type 2 diabetes is associated with dietary advanced glycation end products, Mediterranean diet adherence and oxidative balance score: A pathway analysis.

Büşra Demirer, Hülya Yardımcı, Seda Erem Basmaz.

   AIMS: The aim of this study was to evaluate the effects of dietary advanced glycation end products (dAGE) intake, Mediterranean diet adherence screener (MEDAS), and oxidative balance score (OBS) on inflammation among individuals with type 2 diabetes.
METHODS: The study was conducted with 96 adults (aged between 32 and 64 years) with type 2 diabetes. The average daily dAGE intakes, energy and macronutrient intakes of the participants were taken with the three-day food consumption recording method. OBS and MEDAS score was used. At the same time, routine blood lipids, HbA1c, fasting blood glucose and inflammation marker C-reactive protein (CRP) were measured.
RESULTS: Dietary AGE intake was associated with fasting blood glucose, HbA1c, CRP and blood pressures (p < 0.01). The relationship between OBS and dAGE intake was significant (β = -0.36; 95 % Cl = -0.500, -0.220; p < 0.001). MEDAS has a negative and statistically significant effect on dAGE intake (β = -0.56; 95 % Cl = -0.696, -0.444; p < 0.001). There was a significant and positive effect of dAGE on CRP when other variables (MEDAS, OBS) affecting dAGE were also included in the analysis (β = 0.79; 95 % CI = 0.664, 0.917; p < 0.001).
CONCLUSIONS: Our findings may have important implications for explaining the development of inflammation in type 2 diabetes patients with high dAGE intake.

Keywords:  Diabetes; Dietary advanced glycation end products; Inflammation; Mediterranean diet

DOI:  https://doi.org/10.1016/j.jdiacomp.2022.108354
Front Immunol. 2022 ;13 947147

Inflamed adipose tissue: A culprit underlying obesity and heart failure with preserved ejection fraction.

Chenyu Li, Donglu Qin, Jiarui Hu, Yang Yang, Die Hu, Bilian Yu.

  The incidence of heart failure with preserved ejection fraction is increasing in patients with obesity, diabetes, hypertension, and in the aging population. However, there is a lack of adequate clinical treatment. Patients with obesity-related heart failure with preserved ejection fraction display unique pathophysiological and phenotypic characteristics, suggesting that obesity could be one of its specific phenotypes. There has been an increasing recognition that overnutrition in obesity causes adipose tissue expansion and local and systemic inflammation, which consequently exacerbates cardiac remodeling and leads to the development of obese heart failure with preserved ejection fraction. Furthermore, overnutrition leads to cellular metabolic reprogramming and activates inflammatory signaling cascades in various cardiac cells, thereby promoting maladaptive cardiac remodeling. Growing evidence indicates that the innate immune response pathway from the NLRP3 inflammasome, to interleukin-1 to interleukin-6, is involved in the generation of obesity-related systemic inflammation and heart failure with preserved ejection fraction. This review established the existence of obese heart failure with preserved ejection fraction based on structural and functional changes, elaborated the inflammation mechanisms of obese heart failure with preserved ejection fraction, proposed that NLRP3 inflammasome activation may play an important role in adiposity-induced inflammation, and summarized the potential therapeutic approaches.

Keywords:  HFPEF; NLRP3 inflammasome; inflamed adipose tissue; inflammation; obesity

DOI:  https://doi.org/10.3389/fimmu.2022.947147
Front Physiol. 2022 ;13 1040809

The bidirectional relationship between AMPK pathway activation and myokine secretion in skeletal muscle: How it affects energy metabolism.

Mahdi Ahsan, Léa Garneau, Céline Aguer.

  Myokines are peptides and proteins secreted by skeletal muscle cells, into the interstitium, or in the blood. Their regulation may be dependent or independent of muscle contraction to induce a variety of metabolic effects. Numerous myokines have been implicated in influencing energy metabolism via AMP-activated protein kinase (AMPK) signalling. As AMPK is centrally involved in glucose and lipid metabolism, it is important to understand how myokines influence its signalling, and vice versa. Such insight will better elucidate the mechanism of metabolic regulation during exercise and at rest. This review encompasses the latest research conducted on the relationship between AMPK signalling and myokines within skeletal muscles via autocrine or paracrine signalling.

Keywords:  AMPK; cell signalling; glucose metabolism; lipid metabolism; myokines; skeletal muscle

DOI:  https://doi.org/10.3389/fphys.2022.1040809
JDS Commun. 2022 Nov;3(6): 403-407

Effects of dietary energy density and feeding strategy during the dry period on feed intake, energy balance, milk production, and blood metabolites of Holstein cows.

A Pineda, F C Cardoso, M R Murphy, J K Drackley.

Our study aimed to assess the effects of dietary energy density and strategy of delivery during the dry period on production and metabolic responses of Holstein cows free of displacement of abomasum, retained placenta, metritis, or hypocalcemia. Twenty-seven multiparous cows dried-off 50 d before calving were assigned randomly to 1 of 3 dietary treatments: a controlled energy, high-fiber diet [CE; 1.39 Mcal net energy for lactation (NEL)/kg of dry matter (DM)] formulated to supply 100% of the NEL requirement at ad libitum intake; or a higher energy diet (1.58 Mcal/kg) fed either at ad libitum (HE) or restricted (RE) intake to supply ∼150 or 80% of the NEL requirements, respectively. After calving, all cows were fed the same lactation diet. Cows were individually fed and remained in the study until 28 d postpartum. Data were analyzed using 2 contrasts: CE versus HE (effect of diet composition in cows fed for ad libitum DM intake) and HE versus RE (effect of ad libitum or restricted intake of the same diet). Prepartum intakes of DM and NEL as well as energy balance (EB), were greater for HE than CE and greater for HE than RE. Body weight (BW) gain was higher in HE than in RE, but CE and HE did not differ. Change in body condition score did not differ between CE and HE or HE and RE. Postpartum intakes of DM and NEL, EB, BW, body condition score, calf birth BW, milk yield, and milk components did not differ between CE and HE or HE and RE. Concentrations of glucose, insulin, nonesterified fatty acids, β-hydroxybutyrate, Ca, and Mg pre- and postpartum did not differ among diets. Although sample size was low, dry period plane of energy intake affected prepartum DM intake, EB, and BW gain but did not affect postpartum intakes of DM and NEL, yields of milk and milk components, or blood metabolites in healthy cows.

DOI: https://doi.org/10.3168/jdsc.2022-0233
Front Nutr. 2022 ;9 1012742

Editorial: Muscle mass and function in COVID-19.

Caterina Conte, Maurizio Muscaritoli.



Keywords:  COVID-19; SARS-CoV-2; long-COVID syndrome; muscle; sarcopenia

DOI:  https://doi.org/10.3389/fnut.2022.1012742
Sleep. 2022 Dec 06. pii: zsac295. [Epub ahead of print]

Insufficient sleep predicts poor weight loss maintenance after one year.

Adrian F Bogh, Simon B K Jensen, Christian R Juhl, Charlotte Janus, Rasmus M Sandsdal, Julie R Lundgren, Mikkel H Noer, Nhu Q Vu, Matteo Fiorenza, Bente M Stallknecht, Jens J Holst, Sten Madsbad, Signe S Torekov.

   STUDY OBJECTIVES: Insufficient sleep may attenuate weight loss, but the role of sleep in weight loss maintenance is unknown. Since weight regain after weight loss remains a major obstacle in obesity treatment, we investigated whether insufficient sleep predicts weight regain during weight loss maintenance.
METHODS: In a randomized, controlled, two-by-two factorial study, 195 adults with obesity completed an eight-week low-calorie diet and were randomly assigned to one-year weight loss maintenance with or without exercise and liraglutide 3.0mg/day or placebo. Sleep duration and quality were measured before and after the low-calorie diet and during weight maintenance using wrist-worn accelerometers (GENEActiv) and Pittsburgh Sleep Quality Index. To test associations between insufficient sleep and weight regain, participants were stratified at randomization into subgroups according to sleep duration (</≥6 h/night) or sleep quality (PSQI score ≤/>5).
RESULTS: After a diet-induced 13.1 kg weight loss, participants with short sleep duration at randomization regained 5.3 kg body weight (P=.0008) and had less reduction in body fat percentage compared with participants with normal sleep duration (P=.007) during the one-year weight maintenance phase. Participants with poor sleep quality before the weight loss regained 3.5 kg body weight compared with good quality sleepers (P=.010). During the weight maintenance phase, participants undergoing liraglutide treatment displayed increased sleep duration compared with placebo after 26 weeks (5 vs. -15 min/night) but not after one year. Participants undergoing exercise treatment preserved the sleep quality improvements attained from the initial weight loss.
CONCLUSIONS: Short sleep duration or poor sleep quality was associated with weight regain after weight loss in adults with obesity.

Keywords:  GLP-1 receptor agonist; exercise; obesity; sleep duration; sleep quality; weight loss maintenance

DOI:  https://doi.org/10.1093/sleep/zsac295
Eur J Heart Fail. 2022 Dec 05.

The attack of the clones to the cardiovascular system.

Edoardo Bertero, Christoph Maack.

DOI: https://doi.org/10.1002/ejhf.2748
JCI Insight. 2022 Dec 08. pii: e165469. [Epub ahead of print]

Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84.

Ryuji Ohue-Kitano, Hazuki Nonaka, Akari Nishida, Yuki Masujima, Daisuke Takahashi, Takako Ikeda, Akiharu Uwamizu, Miyako Tanaka, Motoyuki Kohjima, Miki Igarashi, Hironori Katoh, Tomohiro Tanaka, Asuka Inoue, Takayoshi Suganami, Koji Hase, Yoshihiro Ogawa, Junken Aoki, Ikuo Kimura.

  Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. GPR84 acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84-signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited non-alcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage over-activation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake-induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively impreoved NASH in mouse models. Exogenous GPR84 stimulation is therefore a potential strategy for treating NASH.

Keywords:  G proteincoupled receptors; Hepatology; Inflammation; Macrophages

DOI:  https://doi.org/10.1172/jci.insight.165469
Obesity (Silver Spring). 2022 Dec 05.

The association between gut hormones and diet-induced metabolic flexibility in metabolically healthy adults.

Yigit Unlu, Karyne L Vinales, Tim Hollstein, Douglas Chang, Tomás Cabeza de Baca, Mary Walter, Jonathan Krakoff, Paolo Piaggi.

OBJECTIVE: This study investigated whether interindividual variance in diet-induced metabolic flexibility is explained by differences in gut hormone concentrations.
METHODS: A total of 69 healthy volunteers with normal glucose regulation underwent 24-hour assessments of respiratory quotient (RQ) in a whole-room indirect calorimeter during eucaloric feeding (EBL; 50% carbohydrate, 30% fat) and then, in a crossover design, during 24-hour fasting and three normal-protein (20%) overfeeding diets (200% energy requirements). Metabolic flexibility was defined as the change in 24-hour RQ from EBL during standard (50% carbohydrate), high-fat (60%), and high-carbohydrate (75%) overfeeding diets. Plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after an overnight fast were measured prior to and after each diet.
RESULTS: Compared with EBL, on average, 24-hour RQ decreased by ~4% during high-fat overfeeding, whereas it increased by ~4% during standard overfeeding and by ~9% during high-carbohydrate overfeeding. During high-carbohydrate overfeeding, but not during any other overfeeding diet or fasting, increased GLP-1 concentration was associated with increased RQ (r = 0.44, p < 0.001), higher/lower carbohydrate/lipid oxidation rates (r = 0.34 and r = -0.51, both p < 0.01), respectively, and increased plasma insulin concentration (r = 0.38, p = 0.02).
CONCLUSIONS: Increased GLP-1 concentration following high-carbohydrate overfeeding associated with a greater shift to carbohydrate oxidation, suggesting that GLP-1 may be implicated in diet-induced metabolic flexibility to carbohydrate overload.

DOI: https://doi.org/10.1002/oby.23584
J Prev Med Hyg. 2022 Jun;63(2 Suppl 3): E169-E173

Dietary supplements for lipedema.

Gabriele Bonetti, Karen L Herbst, Kristjana Dhuli, Aysha Karim Kiani, Serena Michelini, Silvia Michelini, Maria Rachele Ceccarini, Sandro Michelini, Maurizio Ricci, Marina Cestari, Michela Codini, Tommaso Beccari, Francesco Bellinato, Paolo Gisondi, Matteo Bertelli.

  Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Keywords:  Dietary supplements; Fat burners; Fat burning supplements; Weight loss in lipedema

DOI:  https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2758
BMJ Open Sport Exerc Med. 2022 ;8(4): e001458

Role of physical activity and cardiorespiratory fitness in metabolically healthy obesity: a narrative review.

Zsolt Murlasits, Krisztina Kupai, Zsuzsanna Kneffel.

  Obesity has been associated with a multitude of metabolic disorders, often clustering with risk factors of cardiovascular disease and type 2 diabetes mellitus, hypertension, dyslipidaemia. Overall, obesity is a worldwide, growing health concern. However, a subgroup of obese individuals with a low burden of metabolic abnormalities have been identified and described as metabolically healthy obese (MHO). Whether the MHO phenotype is protective against obesity-related metabolic disorders in the long-term is presently unclear, and current research examining the potential transition has yielded inconsistent results. In this current narrative review, we aim to provide insights on the role of physical activity (PA) and cardiorespiratory fitness (CRF) in MHO. Lifestyle factors such as PA and CRF may influence the MHO phenotype. Limited studies have characterised energy expenditure and CRF in MHO and metabolically unhealthy obese. However, higher levels of PA, less sedentary behaviour and higher CRF have been observed in MHO individuals. Considering the multiple benefits of PA, it is high time to advocate this lifestyle change beyond its influence on energy balance in a weight loss programme to improve cardiovascular and metabolic risk factors irrespective of body weight and fat mass changes. Improved CRF via increased PA, especially exercise participation, while avoiding weight gain is not only a realistic goal, but should be the primary intervention for MHO populations to prevent the transition to an abnormal metabolic state.

Keywords:  Diabetes; Exercise; Obesity

DOI:  https://doi.org/10.1136/bmjsem-2022-001458
Diabetes Obes Metab. 2022 Dec 07.

SGLT-2 Inhibitor Prescribing Practices.

Christopher Alcorn, Prathayini Subarajan, Aditya Kesari, Marie Lockhart, Daryl Cottrell, Kim Jordan.



Keywords:  SGLT2-inhibitor; Type 2 diabetes; cardiovascular disease; heart failure

DOI:  https://doi.org/10.1111/dom.14931
Eur Heart J. 2022 Dec 07. 43(46): 4763-4766

Physical exercise, inflammation, and hypertension: how to improve cardiovascular prevention.

Filippo Crea.

DOI: https://doi.org/10.1093/eurheartj/ehac695
Crit Rev Food Sci Nutr. 2022 Dec 09. 1-27

Dietary restriction in senolysis and prevention and treatment of disease.

Sepideh Aminzadeh-Gohari, Barbara Kofler, Chiara Herzog.

  Aging represents a key risk factor for a plethora of diseases. Targeting detrimental processes which occur during aging, especially before onset of age-related disease, could provide drastic improvements in healthspan. There is increasing evidence that dietary restriction (DR), including caloric restriction, fasting, or fasting-mimicking diets, extend both lifespan and healthspan. This has sparked interest in the use of dietary regimens as a non-pharmacological means to slow aging and prevent disease. Here, we review the current evidence on the molecular mechanisms underlying DR-induced health improvements, including removal of senescent cells, metabolic reprogramming, and epigenetic rejuvenation.

Keywords:  aging; dietary restriction; disease prevention; epigenetics; senescence; senolysis; senolytics

DOI:  https://doi.org/10.1080/10408398.2022.2153355