Explore the vast range of titles available.

Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. Although morphological changes in endurance-trained muscles are well described, the molecular underpinnings of training adaptation are poorly understood. We therefore aimed to elucidate the molecular signature of muscles of trained male mice and unravel the training status-dependent responses to an acute bout of exercise. Our results reveal that, even though at baseline an unexpectedly low number of genes define the trained muscle, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part associated with epigenetic modifications. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor-γ coactivator 1α are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that underpins muscle plasticity in training. The authors explore the molecular signature of skeletal muscle adaptations to an acute bout of exercise in mice, providing a valuable resource that includes transcriptomic, epigenetic, proteomic and phosphoproteomic changes in muscle plasticity.

Dysferlin is a transmembrane protein that plays a prominent role in membrane repair of damaged muscle fibers. Accordingly, mutations in the dysferlin gene cause progressive muscular dystrophies, collectively referred to as dysferlinopathies for which no effective treatment exists. Unexpectedly, experimental approaches that successfully restore membrane repair fail to prevent a dystrophic phenotype, suggesting that additional, hitherto unknown dysferlin-dependent functions contribute to the development of the pathology. Our experiments revealed an altered metabolic phenotype in dysferlin-deficient muscles, characterized by (1) mitochondrial abnormalities and elevated death signaling and (2) increased glucose uptake, reduced glycolytic protein levels, and pronounced glycogen accumulation. Strikingly, elevating mitochondrial volume density and muscle glycogen accelerates disease progression; whereas, improvement of mitochondrial function and recruitment of muscle glycogen with exercise ameliorated functional parameters in a mouse model of dysferlinopathy. Collectively, our results not only shed light on a metabolic function of dysferlin but also imply new therapeutic avenues aimed at promoting mitochondrial function and normalizing muscle glycogen to ameliorate dysferlinopathies, complementing efforts that target membrane repair.

Skeletal muscle possesses extraordinary plasticity of structure, metabolism, and function in response to repeated contractile activity. As a syncytium embedded within a complex microenvironment, muscle relies on the coordination of distinct myonuclear populations and diverse mononucleated cell types. Here, we present a high-resolution single-nucleus RNA-sequencing atlas of 550’000 skeletal muscle nuclei, capturing the longitudinal transcriptional responses of 17 distinct myonuclear and 21 mononuclear cell populations at multiple time points after one bout of exhaustive exercise in trained and sedentary mice. The transcriptional programs of these populations are further shaped by training status into divergent adaptive trajectories. A subset of oxidative myonuclei enters a delayed regenerative state post-exercise, reflecting a bifurcated response to a disproportionate metabolic load on fibers during endurance exercise. Prior training accelerates homeostatic recovery and shields oxidative nuclei from exacerbated damage signatures. In parallel, mononucleated cells emerge as the primary mediators of intercellular communication during recovery. Together, this dataset establishes that training adaptation emerges through a coordinated interplay of intrinsic adaptive programs of multicellular remodeling, and provides a foundational resource for mechanistic insights into muscle plasticity.

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. While morphological changes in endurance-trained muscles are well-described, the molecular underpinnings of training adaptation are poorly understood. We aimed at defining the molecular signature of a trained muscle and unraveling the training status-dependent responses to an acute bout of exercise. Our results reveal that even though at baseline, the transcriptomes of trained and untrained muscles are very similar, training status substantially affects the transcriptional response to an acute challenge, both quantitatively and qualitatively, in part mediated by epigenetic modifications. Second, proteomic changes were elicited by different transcriptional modalities. Finally, transiently activated factors such as the peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha) are indispensable for normal training adaptation. Together, these results provide a molecular framework of the temporal and training status-dependent exercise response that defines muscle plasticity in training.Competing Interest StatementThe authors have declared no competing interest.