bims-mimead 2026-07-19 papers

Life Sci. 2026 Jul 13. pii: S0024-3205(26)00403-0. [Epub ahead of print]402 124594

Impaired mitochondrial flexibility hinders fat pad remodeling in obese mice after 24 h of fasting.

Mariele Lino Silva, Laura Dos Santos Fernandes, Joyce Elisa Heredia, Amanda Carla Clemente de Oliveira, Adma Maciel Babetto, Gustavo de Oliveira Zanetti, Dawit Albieiro Pinheiro Gonçalves, Mauro Martins Teixeira, Geneviève Marcelin, Marina Chaves de Oliveira, Adaliene Versiani Matos Ferreira.

Obesity involves positive energy balance and mitochondrial dysfunction. Mitochondria play a vital role in reshaping tissues by oxidizing substrates; however, tissue-specific organellar plasticity during energy deprivation remains poorly characterized in obesity. We investigated the effects of 24-h fasting on mitochondrial dynamics in adipose tissue, liver, and muscle of lean and diet-induced obese (DIO) male C57BL/6 mice. Fasting reduced body weight by 13% and subcutaneous adipose tissue (SAT) by 40% in lean mice, but only 6.4% in DIO mice, which maintained SAT mass. Indirect calorimetry revealed an attenuated reduction in the respiratory exchange ratio (RER) in DIO mice during the fed-to-fasting transition. In lean mice, fasting triggered tissue-specific mitochondrial morphological adaptations, characterized by increased mitochondrial size in the SAT, liver, and muscle, alongside higher mitochondrial density in the liver. In contrast, DIO mice displayed blunted mitochondrial morphological plasticity. Interestingly, fasting increased endoplasmic reticulum (ER)-mitochondria proximity (MAMs) and modulated mitochondrial chaperone and protease expression in specific tissues of DIO mice. Furthermore, fasted DIO mice showed a downregulation of mtDNA-encoded genes and selected mitochondrial unfolded protein response (UPRmt) markers. In brown adipose tissue (BAT), mitochondrial architecture remained largely unaltered after fasting in both groups. These findings demonstrate that obesity impairs tissue-specific mitochondrial structural adaptations and blunts systemic metabolic flexibility during fasting. Conversely, acute fasting partially promotes ER-mitochondria ultrastructural proximity in obese mice in a tissue-specific manner, establishing a baseline for future functional interventions.

Keywords: Fasting; Mitochondria; Mitochondria-ER interactions; Obesity; Transmission electron microscopy

DOI: https://doi.org/10.1016/j.lfs.2026.124594

Diabetes Metab J. 2026 Jul 15.

Semaglutide and Exercise Synergy in Obesity: Preserving Muscle Mass and Uncovering Organ Crosstalk.

José A Inia, Simone Droog, Jessica Snabel, Aswin L Menke, Martien P M Caspers, Jelle C B C de Jong, J Wouter Jukema, Hans M G Princen, Anita M van den Hoek.

Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, effectively promotes weight loss and improves metabolic parameters in individuals with obesity. However, its use is often accompanied by reductions in lean mass, raising concerns about long-term muscle health. This study explored whether combining semaglutide with exercise could preserve muscle mass and enhance metabolic outcomes.
Methods: Ldlr-/-.Leiden mice with diet-induced obesity, insulin resistance, metabolic dysfunction-associated steatohepatitis and atherosclerosis were either left untreated (control) or treated with semaglutide, exercise or the combination for 14 weeks. Histological and transcriptomic analyses were conducted on adipose tissue, muscle, liver and heart to explore underlying mechanisms.
Results: Semaglutide significantly reduced fat mass (-31%) but also lean mass (-11%). Combining semaglutide with exercise further reduced fat mass (-45%) and lean mass as well but to a lesser extent (-8%). Semaglutide alone or with exercise improved insulin sensitivity and plasma lipids. The combination improved adipose tissue inflammation, liver steatosis, liver inflammation and atherosclerotic lesion area. Only combination treatment significantly improved grip strength and diameter of gastrocnemius myofibers. Multi-organ histological and transcriptomic analyses revealed organ-specific and synergistic effects of combination therapy, including activation of pathways involved in mitochondrial function, glucose metabolism, and inflammation resolution.
Conclusion: Semaglutide improves metabolic, liver, vascular and adipose parameters but reduces lean mass and muscle strength. Combining semaglutide intervention with exercise enhances these benefits with partial preservation of muscle mass and function and activation of distinct molecular pathways not engaged by either monotreatment, thereby underscoring the potential of integrating lifestyle interventions with pharmacological treatment.

Keywords: Exercise; Gene expression profiling; Glucagon-like peptide 1; Life style; Muscular atrophy; Sarcopenia; Semaglutide

DOI: https://doi.org/10.4093/dmj.2025.1060

Exp Physiol. 2026 Jul 17.

Six weeks of high-intensity interval training improve autonomic and metabolic responses in active postmenopausal women.

Jordi Monferrer-Marín, Ainoa Roldán, Jørn Wulff Helge, Cristina Blasco-Lafarga.

This study analysed the effects of a supervised high-intensity interval training (HIIT) programme on metabolic flexibility and autonomic function in active postmenopausal women. Twenty women (66.6 ± 6.2 years; 67.9 ± 11.1 kg) completed a 6-week cycling HIIT intervention consisting of three weekly sessions (20 min/session). Each session included five 1-min bouts at 170-184% of the power output achieved at maximal carbohydrate oxidation (MCO) determined during a submaximal graded FATmax test, interspersed with 1-min active recovery at 0.5 W/kg. The initial 2-week period was included to progressively increase training intensity. Pre- and post-intervention assessments comprised a 30-min basal metabolic rate evaluation with continuous heart rate variability and gas-exchange measurements. Paired comparisons with bar and scatter plots were performed. At MCO intensity, significant improvements were observed in MCO (d = 0.76), V.O2${{\mathop V\limits^{.} }_{{{O}_2}}}$ (d = 1.04), gross and net (d = 1.63; d = 1.35) efficiency, and relative power (d = 2.67), with higher Stress Index (d = 0.72) and blood lactate (d = 0.55). Maximal fat oxidation (MFO) increased from 0.28 to 0.32 g/min (d = 0.51) alongside higher sample-entropy and reduced perceived exertion (d = 0.65, d = 0.80) at MFO intensity, despite no changes in basal metabolic rate or body composition. Changes in V.O2${{\mathop V\limits^{.} }_{{{O}_2}}}$ were negatively correlated with age (R2 = 0.34), whereas net and gross efficiency improvements were positively correlated with this latter (R2 = 0.23 and 0.26). Six weeks of HIIT elicited safe, time-efficient metabolic and autonomic adaptations in postmenopausal women. While power output, V.O2${{\mathop V\limits^{.} }_{{{O}_2}}}$ , carbohydrate oxidation, efficiency and Stress Index improved at MCO intensity, enhanced fat oxidation accompanied by greater autonomic complexity and reduced perceived effort reflect key findings at MFO.

Keywords: autonomic nervous system; fatty acid oxidation; heart rate variability; high intensity interval training; oxygen consumption

DOI: https://doi.org/10.1113/EP093739

J Lipid Res. 2026 Jul 17. pii: S0022-2275(26)00136-7. [Epub ahead of print] 101106

Adults with Obesity and Hyperglycemia have Higher Arachidonic and Docosahexaenoic Acid in Subcutaneous Adipose Tissue.

Sabrina Ziai, Mihir Parikh, Narjes Mosavari, Ruxandra D Rotarescu, Chuck T Chen, Richard P Bazinet, André Tchernof, Anthony J Hanley, Adam H Metherel, Jacqueline L Beaudry.

In obesity, fatty acid (FA) accumulation may impair AT function, promoting insulin resistance and development of type 2 diabetes mellitus (T2DM). However, the contribution of visceral AT (VAT) and subcutaneous AT (SAT) specific FAs to metabolic dysregulation in obesity and T2DM remains unclear, highlighting the importance of examining the FA composition between AT depots. This study examined differences in FA profile and lipid fractions across AT depots in individuals with obesity and hyperglycemia. The primary focus was on polyunsaturated fatty acids (PUFAs) given their relevance to cardiometabolic health. Thirty participant-matching VAT and SAT samples from bariatric surgery donors (BMI ≥ 30 kg/m2) were examined and were further stratified into groups of fasted normoglycemia or hyperglycemia. For the total FA profile, the concentrations (μmol/g) of arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were higher in the SAT compared to VAT depot; ARA and DHA concentrations were higher in the hyperglycemia compared to normoglycemia group. Further analysis in six different lipid fractions including triacylglycerol, diacylglycerol, monoacylglycerol, free fatty acids, phospholipid and cholesteryl esters exhibited similarly higher ARA, EPA, and DHA in the SAT compared to VAT depot. However, differences between normoglycemia and hyperglycemia groups were fraction- and FA-specific, rather than uniform across all lipid classes. These results demonstrate that VAT and SAT depots differentially store FAs as a function of glycemic status in obesity, highlighting distinct differences in PUFA metabolism and availability that may have important implications for AT function and metabolic health.

Keywords: Eicosapentaenoic acid; Fatty Acid Metabolism; Lipids; Omega-3 fatty acids; Phospholipids; Triacylglycerol

DOI: https://doi.org/10.1016/j.jlr.2026.101106