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Skeletal muscle is the largest organ in the human body by mass, making up approximately 40 % of total body weight. Furthermore, it accounts for the majority of insulin-stimulated glucose uptake and is also highly involved in lipid metabolism. Lipids can accumulate in muscle through different distinct depots: as intramyocellular lipids (IMCL), stored as triglyceride-containing droplets within muscle cells and as intermuscular adipose tissue (IMAT), located between muscle fiber bundles beneath the deep muscle fascia. The muscular fat depots have been positively correlated with an increased body fat content in obesity, just like subcutaneous and visceral adipose tissue (SAT and VAT, respectively). IMCL, IMAT, VAT and SAT have additionally been linked to insulin resistance and type 2 diabetes mellitus (T2D).

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Intermittent Time-Restricted Feeding Recapitulates the Physiological Benefits of Daily Time-Restricted Feeding in Male Mice with Chronic Metabolic Disease

Andre Sarmento-Cabral, Marta G. Novelle, Luz Marina Sánchez-Mendoza, Natalia Herman-Sanchez, ... Alberto Diaz-Ruiz

Time-restricted feeding (TRF) is proposed as a relevant strategy to counteract obesity and metabolic disorders; however, the therapeutic efficacy of more pragmatic intermittent TRF (iTRF) regimens remains undefined. Herein, daily and intermittent TRF significantly improved whole-body physiology, promoted key hallmarks of energy restriction, and induced coordinated transcriptional and lipidomic remodeling in male mice with chronic metabolic dysfunction previously established by prolonged high-fat, high-cholesterol, high-fructose feeding. These effects were summarized using three composite scores (physiological/metabolic, energy restriction, and lipidic), which showed consistent associations with each other, suggesting convergence toward a TRF-associated metabolic state across biological scales. Lipidomic profiling identified a subset of hepatic lipids associated with systemic health, pointing to lipid remodeling, particularly at the endoplasmic reticulum, as a potential feature of the TRF response. Notably, TRF failed to histologically improve hepatic steatosis, ballooning, or inflammation, and its overall benefits were clearly inferior to dietary normalization to standard chow diet. Altogether, these data (i) demonstrate that intermittent TRF recapitulates the beneficial effects in advanced metabolic disease, (ii) provides translational support for flexible TRF strategies, and (iii) highlights the need to integrate TRF with additional therapeutic strategies.

Articles in Press

Intermittent Time-Restricted Feeding Recapitulates the Physiological Benefits of Daily Time-Restricted Feeding in Male Mice with Chronic Metabolic Disease

Andre Sarmento-Cabral, Marta G. Novelle, Luz Marina Sánchez-Mendoza, Natalia Herman-Sanchez, ... Alberto Diaz-Ruiz

Time-restricted feeding (TRF) is proposed as a relevant strategy to counteract obesity and metabolic disorders; however, the therapeutic efficacy of more pragmatic intermittent TRF (iTRF) regimens remains undefined. Herein, daily and intermittent TRF significantly improved whole-body physiology, promoted key hallmarks of energy restriction, and induced coordinated transcriptional and lipidomic remodeling in male mice with chronic metabolic dysfunction previously established by prolonged high-fat, high-cholesterol, high-fructose feeding. These effects were summarized using three composite scores (physiological/metabolic, energy restriction, and lipidic), which showed consistent associations with each other, suggesting convergence toward a TRF-associated metabolic state across biological scales. Lipidomic profiling identified a subset of hepatic lipids associated with systemic health, pointing to lipid remodeling, particularly at the endoplasmic reticulum, as a potential feature of the TRF response. Notably, TRF failed to histologically improve hepatic steatosis, ballooning, or inflammation, and its overall benefits were clearly inferior to dietary normalization to standard chow diet. Altogether, these data (i) demonstrate that intermittent TRF recapitulates the beneficial effects in advanced metabolic disease, (ii) provides translational support for flexible TRF strategies, and (iii) highlights the need to integrate TRF with additional therapeutic strategies.

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13th
Helmholtz Diabetes Conference 

Munich, 21-23. Sep 2026                                                                                                                             

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You are what you eat

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