bims-mimead 2026-06-21 papers

Obesity (Silver Spring). 2026 Jun 16.

Dietary Protein Reduction During Isocaloric Conditions Reduces Body Weight in Men With Overweight or Obesity.

Aslak E Lyster, Amalie S Frederiksen, Jacob K Jensen, Annemarie Lundsgaard, Nicoline R Andersen, Kasper S Jørgensen, Daniela Weber, Lukas Nachtigall, Erik A Richter, Andreas M Fritzen, Bente Kiens.

OBJECTIVE: Dietary protein reduction increases plasma fibroblast growth factor 21 (FGF21) and energy requirements in lean men under eucaloric conditions. Whether these metabolic effects translate to weight loss during isocaloric conditions in men with overweight or obesity remains unclear.
METHODS: Seventeen men with overweight or obesity were randomly allocated to two different highly controlled, isocaloric diets for 5 weeks, receiving either a protein-reduced diet (0.9 g kg-1 BW day-1) substituted with increased carbohydrates or a habitual diet (1.8 g kg-1 BW day-1).
RESULTS: Protein reduction induced a 2.0 ± 0.6 kg weight loss and increased plasma FGF21 concentration compared with higher protein intake, without caloric restriction. Changes in plasma FGF21 concentration were inversely associated with changes in body weight (r = -0.59, p = 0.02). Expression of key components in the FGF21 receptor complex, FGFR1 and β-klotho, and downstream targets in subcutaneous adipose tissue remained unchanged. Markers of skeletal muscle mitochondrial oxidative phosphorylation were also unaltered. Fat mass decreased significantly, whereas this level of protein reduction only tended to lower lean body mass.
CONCLUSIONS: These findings suggest that reducing protein intake (0.9 g kg-1 BW day-1), substituted with increased carbohydrates, compared with a habitual protein intake (1.8 g kg-1 BW day-1), can induce weight loss without restricting total energy intake in men with overweight or obesity.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06263725.

Keywords: FGF21; adipose tissue; energy metabolism; protein reduction; weight loss

DOI: https://doi.org/10.1002/oby.70248

Int Rev Cell Mol Biol. 2026 ;pii: S1937-6448(25)00153-4. [Epub ahead of print]404 63-79

Impact of different exercise modalities on mitophagy in human skeletal muscle.

Cristóbal Muñoz-Medina, Alfonso Carriel-Nesvara, Javier Botella, Mauricio Castro-Sepulveda.

Exercise induces profound mitochondrial adaptations in skeletal muscle, with different modalities uniquely influencing different branches of mitochondrial quality control (MQC). This review examines how endurance, resistance, and high-intensity interval training (HIIT) regulate mitophagy, the selective degradation of damaged mitochondria, in skeletal muscle (SkM). Research in rodents has shown that endurance exercise upregulates mitophagy primarily through the AMPK/PGC-1α signaling axis, promoting mitochondrial turnover and ensuring metabolic efficiency. In humans, high-intensity exercise increases mitophagy to a larger extent when compared to traditional endurance exercises. On the other hand, resistance exercise triggers alternative MQC mechanisms, including potential mitochondrial ejection. Collectively, these results suggest that mitophagy and MQC pathways are regulated in human SkM following exercise, but the specific molecular pathways seem to be specific to each exercise mode. Future studies should aim at disentangling the multiple mitophagy and MQC pathways in human SkM following exercise.

Keywords: Aging; Exercise training; Metabolic health; Mitochondrial autophagy; Skeletal muscle plasticity

DOI: https://doi.org/10.1016/bs.ircmb.2025.10.005

Cardiovasc Diabetol. 2026 Jun 16.

Chamber-specific cardiac proteome remodeling in a Göttingen minipig model of obesity and diabetes.

Samantha Gallero, Christian T Voldstedlund, Simone Krog, Trine Pagh Ludvigsen, Lisbeth Høier Olsen, Thomas E Jensen.

BACKGROUND: Obesity and Type 2 Diabetes are major contributors to cardiac hypertrophy and dysfunction, yet the molecular mechanisms driving early myocardial alterations remain incompletely understood. Evidence from rodent models and end-stage human disease suggests that cytoskeletal remodeling and oxidative stress may contribute to early increases in cardiomyocyte stiffness and hypertrophy. Whether these processes are involved at earlier disease stages in translationally relevant large-animal models remains unclear.
METHODS: Heart tissue from male Göttingen minipigs subjected to a 13-month intervention with a standard control diet, high-fat-fructose-cholesterol diet, or high-fat-fructose-cholesterol with streptozotocin-induced diabetes was analyzed. Untargeted proteomics was performed on left atrium and left ventricle tissue, followed by pathway enrichment analyses to identify diet- and chamber-specific proteomic alterations.
RESULTS: Global proteomic analyses revealed that anatomical region represented the dominant source of variance, with ~ 200-300 proteins significantly regulated across dietary interventions. Pathway enrichment analyses highlighted alterations in protein and macronutrient metabolism, mitochondrial function, and extracellular matrix organization. Correlation and Hallmark analyses further linked ventricular remodeling to glucose-associated and mitochondrial pathways, while atrial remodeling was more closely associated with metabolic and nutrient-sensing pathways. Among 75 microtubule and 53 redox-related proteins examined, 16 and 14, respectively, were significantly altered in a chamber- and intervention-dependent manner.
CONCLUSION: Early cardiac hypertrophy associated with obesity and/or diabetes is accompanied by extensive proteomic remodeling, characterized by distinct atrial and ventricular profiles. However, the relatively modest changes in microtubule and redox-related proteins suggest that these are unlikely to be primary drivers of early myocardial remodeling.

DOI: https://doi.org/10.1186/s12933-026-03250-9

Physiol Rep. 2026 Jun;14(12): e70876

Higher whole-body and exogenous postprandial glucose oxidation in the luteal versus follicular phase in healthy females.

Alexa Govette, Daniel W D West, Madeleine Pettit, Eric Antonen, Anessa Koussiouris, Daniel R Moore, Jenna B Gillen.

Menstrual cycle phase can influence indices of carbohydrate metabolism at rest and during exercise; however, limited research has explored whether there are menstrual phase-specific differences in substrate metabolism in response to oral feeding. Using a within-subjects crossover design, 15 eumenorrheic females completed a metabolic trial in the follicular phase (FP; day 7 ± 2) and the luteal phase (LP; day 22 ± 3; 8 ± 2 days post-ovulation) of a single menstrual cycle. Following an overnight fast, participants consumed a 75 g glucose beverage enriched with a [U-13C6] D-glucose tracer. Capillary glucose concentrations, exogenous glucose oxidation, expired carbon dioxide percentage (L%CO2), and whole-body carbohydrate and fat oxidation rates were measured fasted and across 3-h postprandially. Peak 3-h glucose concentration was higher in LP versus FP (p = 0.04), with no differences in 3-h mean glucose or incremental area under the curve between phases (p = 0.34-0.63). Whole-body (p = 0.03) and exogenous carbohydrate oxidation (p = 0.002) were higher in LP versus FP. %LCO2 was elevated above fasting at all postprandial timepoints (p < 0.001) with no differences between phases (p = 0.84). In conclusion, following an oral glucose load, peak blood glucose concentration and carbohydrate oxidation rates were elevated in LP versus FP. These findings suggest postprandial substrate utilization differs by menstrual cycle phase in healthy females.

Keywords: blood glucose; carbohydrate oxidation; estradiol; fat oxidation; substrate utilization

DOI: https://doi.org/10.14814/phy2.70876

Nat Rev Cardiol. 2026 Jun 16.

Role of systemic and epicardial adipose tissue in cardiometabolic disease.

Shaun Khanna, Gurkeerat Mann, Aditya Bhat, Andrew Lin, Anushka Patel, Stephen J Nicholls, Andrew Sindone, Damini Dey, Deepak L Bhatt, Clare Arnott, Thomas H Marwick, Nitesh Nerlekar.

Adipose tissue is increasingly recognized as an immunological and metabolic organ composed of multiple specialized depots that exert diverse effects on cardiometabolic health. Beyond total adiposity, the distribution and phenotypic state of regional adipose tissue depots, including visceral, subcutaneous and epicardial adipose tissue, contribute to shaping overall cardiovascular risk. These depots communicate with the vasculature and myocardium through endocrine, paracrine, vasocrine and neural pathways to mediate cardiovascular inflammation and remodelling. Advances in cardiac CT, MRI, dual-energy X-ray absorptiometry and artificial intelligence technologies in the past 5 years have resulted in highly reproducible measurements of adipose tissue volume, quality, density and radiomics. Emerging multiomics data now reveal how specific adipose tissue patterns correspond to pathways of inflammation and the development of cardiovascular disease. In this Review, we synthesize the current evidence across adipose depots, highlighting how their collective biology, more so than quantity alone, shapes cardiometabolic risk. Furthermore, we highlight emerging insights into adipose depot-specific biology, imaging phenotyping, ethnicity-related and sex-related differences, and potential therapeutic modulation. We also introduce the 'unified adipose tissue' model that conceptualizes all adipose tissue depots as components of a unified system, in which the biology rather than the total mass of adipose tissue drives cardiometabolic disease.

DOI: https://doi.org/10.1038/s41569-026-01304-9