Abstract
Obesity is a chronic, complex pathology associated with a risk of developing secondary pathologies, including cardiovascular diseases, cancer, type 2 diabetes (T2DM) and musculoskeletal disorders. Since skeletal muscle accounts for more than 70% of total glucose disposal, metabolic alterations are strictly associated with the onset of insulin resistance and T2DM. The present study relies on the proteomic analysis of gastrocnemius muscle from 15 male and 15 female C56BL/J mice fed for 14 weeks with standard, 45% or 60% high-fat diets (HFD) adopting a label-free LC–MS/MS approach followed by bioinformatic pathway analysis. Results indicate changes in males due to HFD, with increased muscular stiffness (Col1a1, Col1a2, Actb), fiber-type switch from slow/oxidative to fast/glycolytic (decreased Myh7, Myl2, Myl3 and increased Myh2, Mylpf, Mybpc2, Myl1), increased oxidative stress and mitochondrial dysfunction (decreased respiratory chain complex I and V and increased complex III subunits). At variance, females show few alterations and activation of compensatory mechanisms to counteract the increase of fatty acids. Bioinformatics analysis allows identifying upstream molecules involved in regulating pathways identified at variance in our analysis (Ppargc1a, Pparg, Cpt1b, Clpp, Tp53, Kdm5a, Hif1a). These findings underline the presence of a gender-specific response to be considered when approaching obesity and related comorbidities.
Highlights
Obesity incidence has dramatically increased, reaching pandemic proportions with a rising trend until 2030 [1]
This study aims to characterize the proteomic profile of skeletal muscles of dietinduced obesity (DIO) animal models fed with high-fat diets at the different fat content
Animals fed for 14 weeks with two high-fat diets (HFD) regimens (45 kcal% and 60 kcal% fat content diets; 45% HFD and 60% HFD, respectively) showed increased body weight compared to a control group (CTR) fed with a standard (10 kcal% fat content) diet (Figure 1a)
Summary
Obesity incidence has dramatically increased, reaching pandemic proportions with a rising trend until 2030 [1]. Obesity is due to an abnormal fat accumulation resulting from a long-term energy imbalance between caloric intake and energy expenditure [2,3] It is a chronic and complex pathological condition associated with cardiovascular diseases, cancer, type 2 diabetes mellitus and musculoskeletal disorders, like sarcopenia [4] and tendinopathies. Dysfunctional organelles promote the release of FFAs and their intermediates (e.g., diacylglycerol, linoleic, phosphatidic and lysophosphatidic acids and ceramides), proinflammatory molecules and ROS. The increase of these molecules in the bloodstream [17,18] can develop a low-grade systemic inflammation that determines the onset of insulin resistance [19]
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