bims-kimdis 2023-12-24 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023–12–24
fiveteen papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins

A ketogenic diet reduces age-induced chronic neuroinflammation in mice.
Unraveling the complex connection between ketone bodies and insulin resistance.
Impact of ketogenic diet on cardiovascular disease.
Muscle immune cells protect mitochondrial organelles during exercise.
Evaluating the efficacy of a ketogenic diet in managing drug resistant paediatric DEDPC5-related epilepsy.
SLC16a6, mTORC1, and Autophagy Regulate Ketone Body Excretion in the Intestinal Cells.
Ketogenic diet alleviates β-cell dedifferentiation but aggravates hepatic lipid accumulation in db/db mice.
Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.
Effects of duration of uninterrupted fast in weekly intermittent fasting: Comparison of an 82-week 5:2 case report to an isocaloric modified 4:3 protocol.
A low-carbohydrate diet in place of SGLT2i therapy in a patient with diabetic cardiomyopathy.
Intact Short, Intermediate, and Long Skeletal Muscle Fibers Obtained by Enzymatic Dissociation of Six Hindlimb Muscles of Mice: Beyond Flexor Digitorum Brevis.
A very-low-carbohydrate diet for minimising blood glucose excursions during ultra-endurance open-water swimming in type 1 diabetes: a case report.
The Effects of Different Types of Diets on Steroid Hormone Concentrations.
Does the Menstrual Cycle Influence Aerobic Capacity in Endurance-Trained Women?
The anabolic response to protein ingestion during recovery from exercise has no upper limit in magnitude and duration in vivo in humans.

bioRxiv. 2023 Dec 04. pii: 2023.12.01.569598. [Epub ahead of print]

A ketogenic diet reduces age-induced chronic neuroinflammation in mice.

Mitsunori Nomura, Natalia Faraj Murad, Sidharth S Madhavan, Brenda Eap, Thelma Y Garcia, Carlos Galicia Aguirre, Eric Verdin, Lisa Ellerby, David Furman, John C Newman.

Beta-hydroxybutyrate (BHB) is a ketone body synthesized during fasting or strenuous exercise. Our previous study demonstrated that a cyclic ketogenic diet (KD), which induces BHB levels similar to fasting every other week, reduces midlife mortality and improves memory in aging mice. BHB actively regulates gene expression and inflammatory activation through non-energetic signaling pathways. Neither of these activities has been well-characterized in the brain and they may represent mechanisms by which BHB affects brain function during aging. First, we analyzed hepatic gene expression in an aging KD-treated mouse cohort using bulk RNA-seq. In addition to the downregulation of TOR pathway activity, cyclic KD reduces inflammatory gene expression in the liver. We observed via flow cytometry that KD also modulates age-related systemic T cell functions. Next, we investigated whether BHB affects brain cells transcriptionally in vitro . Gene expression analysis in primary human brain cells (microglia, astrocytes, neurons) using RNA-seq shows that BHB causes a mild level of inflammation in all three cell types. However, BHB inhibits the more pronounced LPS-induced inflammatory gene activation in microglia. Furthermore, we confirmed that BHB similarly reduces LPS-induced inflammation in primary mouse microglia and bone marrow-derived macrophages (BMDMs). BHB is recognized as an inhibitor of histone deacetylase (HDAC), an inhibitor of NLRP3 inflammasome, and an agonist of the GPCR Hcar2. Nevertheless, in microglia, BHB's anti-inflammatory effects are independent of these known mechanisms. Finally, we examined the brain gene expression of 12-month-old male mice fed with one-week and one-year cyclic KD. While a one-week KD increases inflammatory signaling, a one-year cyclic KD reduces neuroinflammation induced by aging. In summary, our findings demon-strate that BHB mitigates the microglial response to inflammatory stimuli, like LPS, possibly leading to decreased chronic inflammation in the brain after long-term KD treatment in aging mice.

DOI: https://doi.org/10.1101/2023.12.01.569598
Acta Physiol (Oxf). 2023 Dec 22. e14077

Unraveling the complex connection between ketone bodies and insulin resistance.

Patrycja Puchalska.

DOI: https://doi.org/10.1111/apha.14077
Nutr Rev. 2023 Dec 18. pii: nuad152. [Epub ahead of print]

Impact of ketogenic diet on cardiovascular disease.

Mohamed S Zaghloul, Santiago Elizondo-Benedetto, Mohamed A Zayed.

   OBJECTIVES: A comprehensive review of the current literature was conducted to summarize the potential therapeutic and management roles of ketogenic diet (KD) for cardiovascular disease (CVD).
BACKGROUND: Consensus has not been reached on the optimal diet for individuals with cardiovascular risk factors. KDs are characterized by high-fat, low-carbohydrate, and appropriate protein content, and have gained popularity in recent years in the management of various conditions, including cardiovascular and metabolic diseases.
METHODS: Original research, systematic reviews, and meta-analyses available in the PubMed, Web of Science, and Google Scholar databases were reviewed.
RESULTS: The current body of preclinical and clinical evidence on the efficacy of KD in the management of CVD remains limited. Specific applications of KD seem to suggest a positive impact on management of CVD. However, conflicting results and a lack of precise molecular and biochemical mechanisms of action provide ample opportunity for future investigation.
CONCLUSION: More multidisciplinary studies are needed to determine the true clinical benefit of KD in the management of CVD and so justify its expanded clinical use.

Keywords:  atherosclerosis; cardiovascular diseases; ketogenic diet; life style; nutrition

DOI:  https://doi.org/10.1093/nutrit/nuad152
Nature. 2024 Jan;625(7993): 35-36

Muscle immune cells protect mitochondrial organelles during exercise.

Gerald Coulis, S Armando Villalta.



Keywords:  Cell biology; Immunology; Physiology

DOI:  https://doi.org/10.1038/d41586-023-03972-w
Epilepsy Behav. 2023 Dec 19. pii: S1525-5050(23)00454-7. [Epub ahead of print]150 109535

Evaluating the efficacy of a ketogenic diet in managing drug resistant paediatric DEDPC5-related epilepsy.

Anna Winczewska-Wiktor, Małgorzata Braszka, Mia Harada-Laszlo, Magdalena Badura-Stronka, Izabela Kaczmarek, Monika Starczewska, Agnieszka Wencel-Warot, Barbara Steinborn, Aleksander Jamsheer.

   AIM: To evaluate the effectiveness of the ketogenic diet treatment in a cohort of patients with drug-resistant epilepsy with a mutation in the DEPDC5 gene.
MATERIALS AND METHODS: We followed four paediatric patients with drug resistant DEPDC5-related epilepsy through a ketogenic diet (KD) treatment course. We analyzed the following parameters of their clinical profiles: past medical history, clinical characteristics of seizure morphology, EEG records pre- and post-KD treatment, the results of MRI head and neurological and psychological examinations (pre-treatment and throughout treatment course). We evaluated the effectiveness of previous therapeutic approaches and the current treatment with ketogenic diet alongside results of neuroimaging studies. Effect of KD on co-morbid behavioural and psychiatric symptoms, as well as adverse effects from KD were also assessed.
RESULTS: In three patients, the introduction of the ketogenic diet resulted in the cessation of seizures, while in 1 patient with co-morbid cortical dysplasia, epileptic seizures of lesser severity returned after an initial seizure-free period of several weeks. Further, 1 patient was able to transition to a KD-only treatment regimen. The remaining patients were able to reduce the number of antiseizure medicine (ASM) to a monotherapy. In all cases we observed improvements in EEG results. Our cohort included one patient whose MRI head showed cortical dysplasia. However, no patients demonstrated any neurological signs in neurological examination. Psychological examination showed normal intellectual development in all patients, although behavioral disorders and difficulties at school were observed. The introduction of KD treatment correlated with improvement in school performance and improved behavioral regulation. No clinically significant adverse events were observed.
CONCLUSIONS: KD seems to be both effective and well tolerated in young patients with DEPDC5-related epilepsy, both as a monotherapy and as an adjunct to ASM. We recommend an early adoption of this therapeutic approach in this patient demographic. Our results demonstrate that the positive effects of KD treatment encompass improvements in general functioning, particularly in the context of school performance and behavior, in addition to the achievement of good seizure control.

Keywords:  DEPDC5; Epilepsy; Ketogenic diet; mTOR

DOI:  https://doi.org/10.1016/j.yebeh.2023.109535
Biology (Basel). 2023 Nov 26. pii: 1467. [Epub ahead of print]12(12):

SLC16a6, mTORC1, and Autophagy Regulate Ketone Body Excretion in the Intestinal Cells.

Takashi Uebanso, Moeka Fukui, Chisato Naito, Takaaki Shimohata, Kazuaki Mawatari, Akira Takahashi.

  Ketone bodies serve several functions in the intestinal epithelium, such as stem cell maintenance, cell proliferation and differentiation, and cancer growth. Nevertheless, there is limited understanding of the mechanisms governing the regulation of intestinal ketone body concentration. In this study, we elucidated the factors responsible for ketone body production and excretion using shRNA-mediated or pharmacological inhibition of specific genes or functions in the intestinal cells. We revealed that a fasting-mimicked culture medium, which excluded glucose, pyruvate, and glutamine, augmented ketone body production and excretion in the Caco2 and HT29 colorectal cells. This effect was attenuated by glucose or glutamine supplementation. On the other hand, the inhibition of the mammalian target of rapamycin complex1 (mTORC1) recovered a fraction of the excreted ketone bodies. In addition, the pharmacological or shbeclin1-mediated inhibition of autophagy suppressed ketone body excretion. The knockdown of basigin, a transmembrane protein responsible for targeting monocarboxylate transporters (MCTs), such as MCT1 and MCT4, suppressed lactic acid and pyruvic acid excretion but increased ketone body excretion. Finally, we found that MCT7 (SLC16a6) knockdown suppressed ketone body excretion. Our findings indicate that the mTORC1-autophagy axis and MCT7 are potential targets to regulate ketone body excretion from the intestinal epithelium.

Keywords:  autophagy; intestinal cell; ketone body; mTORC1; solute carrier family 16 member 6: SLC16a6 (MCT7)

DOI:  https://doi.org/10.3390/biology12121467
Nutrition. 2023 Oct 31. pii: S0899-9007(23)00312-X. [Epub ahead of print]119 112284

Ketogenic diet alleviates β-cell dedifferentiation but aggravates hepatic lipid accumulation in db/db mice.

Mengxiao Zhang, Yu Chen, Shuoshuo Sun, Shaohong Zhang, Li Yuan, Yijiao Xu, Xingjia Li, Guofang Chen, Xiao Wei, Chao Liu.

   OBJECTIVE: The aim of this study was to explore the effect of the ketogenic diet (KD) on β-cell dedifferentiation and hepatic lipid accumulation in db/db mice.
METHODS: After a 3-wk habituation, male db/db mice ages 8 wk were assigned into one of three groups: normal diet (ND), KD, and 75% calorie restriction (CR) group. Free access to a standard diet, a KD, and 75% of a standard diet, respectively, were given to each group. Additionally, sex-matched 8-wk-old C57BL/6 mice were used to construct a control (C) group. After a 4-wk dietary intervention, mouse body weight, fasting blood glucose (FBG), blood lipids, fasting insulin (FINS), glucose tolerance, and β-hydroxybutyric acid level were measured. The morphologies of the islet and liver were observed by hematoxylin and eosin staining. Positive expressions of β-cell-specific transcription factors in mouse islets were determined by double immunofluorescence staining. The size and number of lipid droplets in mouse liver were examined by Oil Red O staining. Real-time quantitative reverse transcription polymerase chain reaction detected relative levels of adipogenesis-associated and lipolysis-associated genes in mouse liver. Additionally, expressions of CD36 protein in the mouse liver were determined by immunohistochemical staining and Western blot.
RESULTS: After a 4-wk dietary intervention, FBG, FINS, and glucose area under the curve in the KD group became significantly lower than in the ND group (all P < 0.05). Regular morphology of mouse islets was observed in the KD group, with an increased number of islet cells. The KD significantly reversed the decrease in β-cell number, disarrangement of β-cells, decline of β/α-cell ratio, and downregulation of β-cell-specific transcription factors in db/db mice. Serum levels of triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol were comparable between the ND and KD groups. In contrast, serum triacylglycerol levels were significantly lower in the CR group than in the ND group (P < 0.05). Vacuolar degeneration and lipid accumulation in the liver were more prominent in the KD group than in the ND and CR groups. The mRNA levels of Pparα and Acox1 in the KD group were lower than those in the ND group, although no significant differences were detected. Relative levels of Cd36 and inflammatory genes in the mouse liver were significantly higher in the KD group than in the ND group (all P < 0.05).
CONCLUSION: The KD significantly reduced FBG and FINS and improved glucose tolerance in db/db mice by upregulating β-cell-specific transcription factors and reversing β-cell dedifferentiation. However, the KD also induced hepatic lipid accumulation and aggravated inflammatory response in the liver of db/db mice.

Keywords:  Hepatic lipid accumulation; Ketogenic diet; Type 2 diabetes mellitus; β-cell dedifferentiation

DOI:  https://doi.org/10.1016/j.nut.2023.112284
Cell Metab. 2023 Dec 14. pii: S1550-4131(23)00449-7. [Epub ahead of print]

Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.

Riley J Wedan, Jacob Z Longenecker, Sara M Nowinski.

  Contrary to their well-known functions in nutrient breakdown, mitochondria are also important biosynthetic hubs and express an evolutionarily conserved mitochondrial fatty acid synthesis (mtFAS) pathway. mtFAS builds lipoic acid and longer saturated fatty acids, but its exact products, their ultimate destination in cells, and the cellular significance of the pathway are all active research questions. Moreover, why mitochondria need mtFAS despite their well-defined ability to import fatty acids is still unclear. The identification of patients with inborn errors of metabolism in mtFAS genes has sparked fresh research interest in the pathway. New mammalian models have provided insights into how mtFAS coordinates many aspects of oxidative mitochondrial metabolism and raise questions about its role in diseases such as obesity, diabetes, and heart failure. In this review, we discuss the products of mtFAS, their function, and the consequences of mtFAS impairment across models and in metabolic disease.

Keywords:  fatty acids; inborn errors of metabolism; lipid metabolism; lipids; mitochondria; mitochondrial fatty acid synthesis; mouse models; mtFAS

DOI:  https://doi.org/10.1016/j.cmet.2023.11.017
Res Sq. 2023 Dec 07. pii: rs.3.rs-3701752. [Epub ahead of print]

Effects of duration of uninterrupted fast in weekly intermittent fasting: Comparison of an 82-week 5:2 case report to an isocaloric modified 4:3 protocol.

Katarina Borer.

Intermittent fasting (IF) approach for weight loss obviates the inconvenience of calorie counting of daily caloric restriction (DCR). It tests IF ability to better counteract a metabolic defense mechanism (MDM) than DCR. MDM obstructs weight loss and facilitates weight regain possibly by increasing hunger and efficiency of exercise energy expenditure (EEf), and by reducing resting metabolic rate (RMR) and physical activity (PA). A knowledge gap exists about whether the duration of weekly uninterrupted fasts (UFs), where the IF protocols are isocaloric, mitigate the MDM. This study compares two IF protocols that have the same weekly number of hours of fast (108) and free access to food (60), but which differ in the duration of UF. An 82-week case report was conducted with twice-weekly near-absolute 36-hour fasts on non-consecutive days (5:2-NC) and compared to ten studies with a 20-hour UF on three non-consecutive days (4:3-NC) modified through provision of a 500-600 kcal meal on fasting days. The large meal raised insulin concentration for 4 hours and reduced the UF to 8 hours followed by 12 nocturnal hours of fasting. The hypotheses were that (1) because of their matched F/E ratio, the rates of weight and fat losses will be similar in both protocols, and (2) because of its longer UF period, hunger will be higher and RMR and voluntary physical activity lower, in 5:8-NC than in M4:3-NC protocol,. The main differences between the two protocols were, (1) slower rates of weight and fat losses, (2) lower sensation of hunger and substantial decline in fullness, no change in RMR and physical activity, and 2.5 times higher post-fast concentration of the ketone body beta-hydroxybutyrate (BHB) in 8:2-NC compared to M4:3-NC protocol. Absence of increased hunger and the variability of the rate of weight loss in 5:2-NC protocol, plus increased EEf in one M4:3-NC study suggest that IF does not curtail MDM, but shortened UF period in M4:3-NC reduces elicitation of BHB. Thus, the addition of a large meal on fasting days is unnecessary for prevention of hunger and is counterproductive for increases in BHB and its potential health benefits.

DOI: https://doi.org/10.21203/rs.3.rs-3701752/v1
Endocrinol Diabetes Metab Case Rep. 2023 Oct 01. pii: 23-0086. [Epub ahead of print]2023(4):

A low-carbohydrate diet in place of SGLT2i therapy in a patient with diabetic cardiomyopathy.

Sabine Kleissl-Muir, Bodil Rasmussen, Alice Owen, Caryn Zinn, Andrea Driscoll.

Summary: In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF). Referred to as diabetic cardiomyopathy (DMCM), this syndrome often exists in the absence of conventional risk factors for HF such as history of myocardial infarction or hypertension. Low-carbohydrate diets (LCDs) have recently been endorsed as an efficacious therapeutic dietary approach to prevent and reverse cardiometabolic disease including type 2 diabetes mellitus (T2DM). LCDs improve systemic insulin resistance (IR), reverses cardiac remodelling in a rodent model and downregulates the expression of sodium-glucose co-transporter 2 (SGLT2) receptors in the kidney. It is therefore conceivable that a lifestyle approach such as adopting an LCD can be offered to patients with DMCM. The reported case is that of a 45-year-old man with a 15-year history of non-ischaemic cardiomyopathy, T2DM and obesity. The patient volunteered to engage in a 16-week low-carbohydrate dietary intervention trial and then self-selected to remain on this diet for 1 year. The whole-food LCD was based on simple 'traffic light' style food lists and not designed to restrict calories, protein, fat or salt. After 1 year, the patient had lost 39 kg and his cardiometabolic markers had significantly improved. LCDs present a potentially beneficial approach for patients with DMCM and could be considered as a lifestyle intervention before SGLT2i therapy is commenced.
Learning points: Diabetic cardiomyopathy (DMCM) is a syndrome precipitated mainly by the detrimental effects of glucose metabolism disorders such as insulin resistance and diabetes. Low-carbohydrate diets (LCD) mimic many effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i). LCDs are a dietary pattern which can have significant and beneficial effects on metabolic and anthropometric markers in patients with DMCM. LCDs and SGLT2i therapy could be combined and may achieve better clinical outcomes for patients with DMCM. Combination therapy may be carried out under close supervision as the real risk for diabetic ketoacidosis remains.

DOI: https://doi.org/10.1530/EDM-23-0086
J Vis Exp. 2023 Dec 01.

Intact Short, Intermediate, and Long Skeletal Muscle Fibers Obtained by Enzymatic Dissociation of Six Hindlimb Muscles of Mice: Beyond Flexor Digitorum Brevis.

Jorge L Petro, Andrés F Milán, Erika Arenas, Laura Valle, Valeria Hernández, Juan C Calderón.

Skeletal muscle fibers obtained by enzymatic dissociation of mouse muscles are a useful model for physiological experiments. However, most papers deal with the short fibers of the flexor digitorum brevis (FDB), which restrains the scope of results dealing with fiber types, limits the amount of biological material available, and impedes a clear connection between cellular physiological phenomena and previous biochemical and dynamical knowledge obtained in other muscles. This paper describes how to obtain intact fibers from six muscles with different fiber type profiles and lengths. Using C57BL/6 adult mice, we show the muscle dissection and fiber isolation protocol and demonstrate the suitability of the fibers for Ca2+ transient studies and their morphometric characterization. The fiber type composition of the muscles is also presented. When dissociated, all muscles rendered intact, living fibers that contract briskly for more than 24 h. FDB gave short (<1 mm), peroneus digiti quarti (PDQA) and peroneus longus (PL) gave intermediate (1-3 mm), while extensor digitorum longus (EDL), extensor hallucis longus (EHL), and soleus muscles released long (3-6 mm) fibers. When recorded with the fast dye Mag-Fluo-4, Ca2+ transients of PDQA, PL, and EHL fibers showed the fast, narrow kinetics reminiscent of the morphology type II (MT-II), known to correspond to type IIX and IIB fibers. This is consistent with the fact that these muscles have over 90% of type II fibers compared with FDB (~80%) and soleus (~65%). Moving beyond FDB, we demonstrate for the first time the dissociation of several muscles, which render fibers spanning a range of lengths between 1 and 6 mm. These fibers are viable and give fast Ca2+ transients, indicating that the MT-II can be generalized to IIX and IIB fast fibers, regardless of their muscle source. These results increase the availability of models for mature skeletal muscle studies.

DOI: https://doi.org/10.3791/65851
Appl Physiol Nutr Metab. 2023 Dec 18.

A very-low-carbohydrate diet for minimising blood glucose excursions during ultra-endurance open-water swimming in type 1 diabetes: a case report.

Shania Smee, Rebecca Johnson, Amy Rush, Raymond J Davey.

Carbohydrate-restricted diets are used by people with type 1 diabetes (T1D) to help manage their condition. However, the impact of this strategy on blood glucose responses to exercise is unknown. This study describes the nutritional strategies of an athlete with T1D, who follows a very-low-carbohydrate diet to manage her condition during an ultra-endurance open-water swimming event. The athlete completed the 19.7km distance in 6-hours 43-minutes. She experienced minimal disruptions to glycaemia, reduced need for supplemental carbohydrate, and no episodes of symptomatic hypoglycaemia. This case report will hopefully encourage further experimental studies that inform and expand current clinical practice guidelines.

DOI: https://doi.org/10.1139/apnm-2023-0266
Physiol Res. 2023 Dec 17. 72(S4): S323-S337

The Effects of Different Types of Diets on Steroid Hormone Concentrations.

M Dušková.

The great popularity of various diets in recent years has led us to reflect on their suitability for our health. The aim of this communication is to review current knowledge on the influence of the most well-known diets on the concentrations of the main steroids and to consider possible mechanisms. The influence of diet on hormone concentrations is expected, but the literature data on this topic are inconsistent and yield conflicting results. The main problem in evaluating these influences is the change in weight that a change in diet induces. This effect needs to be filtered out in order to discover interesting associations between diet and steroid hormones. This is illustrated by the example of the effects of ketogenic diets on testosterone levels in men, where the direct effect of the diet is to reduce testosterone levels, but a number of papers have described increases that are due to diet-related weight loss and the modification of obesity-induced changes. A second major driver is the change in circadian rhythm, and it is necessary to assess hormonal changes induced by changing the time of day of the diet. Such shifts within the circadian rhythm rather than due to a particular type of diet itself are documented by changes in the circadian rhythm of cortisol.
Res Q Exerc Sport. 2023 Dec 18. 1-8

Does the Menstrual Cycle Influence Aerobic Capacity in Endurance-Trained Women?

Sofie Ekberg, Bente Morseth, Karin B Larsén, Lisbeth Wikström-Frisén.

  Purpose: The aim was to study if aerobic capacity varies during different phases of the menstrual cycle (MC) in endurance-trained female athletes. Methods: Ten endurance-trained eumenorrheic women performed a submaximal test followed by an incremental test until exhaustion three times during one MC, early follicular phase (EFP), late follicular phase (LFP), and midluteal phase (MLP). During the submaximal test, the respiratory exchange ratio (RER) and utilization of fat and carbohydrates were analyzed; and, during the incremental test, VO2 peak, maximal heart rate, utilization of fat and carbohydrates, and RER were analyzed. Lactate levels were analyzed at rest, during the submaximal test, and after the incremental test. The anaerobic threshold was determined at RER = 1. Results: No significant differences (p < .05) between the MC phases were seen in a maximal heart rate or VO2peak. Similarly, VO2, heart rate, RER, fatty acid oxidation, and carbohydrate oxidation at 70, 80, 90, and 100% of VO2peak did not differ significantly between MC phases. There were no significant differences between these phases in resting lactate before the test or during the submaximal tests, though there was a significant difference in lactate concentration 3 minutes after the incremental test between the EFP and the LFP (p = .043). Conclusion: This study did not display variations in physiological parameters between EFP, LFP, and MLP, indicating similar aerobic capacity despite hormonal variations. This knowledge may be useful when planning for competition in aerobic events.

Keywords:  Aerobic capacity; female sex hormones; incremental test; menstrual cycle; sports physiology

DOI:  https://doi.org/10.1080/02701367.2023.2291473
Cell Rep Med. 2023 Dec 19. pii: S2666-3791(23)00540-2. [Epub ahead of print]4(12): 101324

The anabolic response to protein ingestion during recovery from exercise has no upper limit in magnitude and duration in vivo in humans.

Jorn Trommelen, Glenn A A van Lieshout, Jean Nyakayiru, Andrew M Holwerda, Joey S J Smeets, Floris K Hendriks, Janneau M X van Kranenburg, Antoine H Zorenc, Joan M Senden, Joy P B Goessens, Annemie P Gijsen, Luc J C van Loon.

  The belief that the anabolic response to feeding during postexercise recovery is transient and has an upper limit and that excess amino acids are being oxidized lacks scientific proof. Using a comprehensive quadruple isotope tracer feeding-infusion approach, we show that the ingestion of 100 g protein results in a greater and more prolonged (>12 h) anabolic response when compared to the ingestion of 25 g protein. We demonstrate a dose-response increase in dietary-protein-derived plasma amino acid availability and subsequent incorporation into muscle protein. Ingestion of a large bolus of protein further increases whole-body protein net balance, mixed-muscle, myofibrillar, muscle connective, and plasma protein synthesis rates. Protein ingestion has a negligible impact on whole-body protein breakdown rates or amino acid oxidation rates. These findings demonstrate that the magnitude and duration of the anabolic response to protein ingestion is not restricted and has previously been underestimated in vivo in humans.

Keywords:  absorption; autophagy; bioavailability; de novo; digestion; intermittent fasting; mTOR; meal frequency; protein requirements; time-restricted feeding

DOI:  https://doi.org/10.1016/j.xcrm.2023.101324