Proteomic Analysis of Skeletal Muscle and White Adipose Tissue after Aerobic Exercise Training in High Fat Diet Induced Obese Mice

Abstract

Obesity is associated with excessive fat accumulation in adipose tissue and other organs, such as skeletal muscle, whereas aerobic exercise (AE) plays an important role in managing obesity through profound protein regulation. Our study aimed to investigate the impact of AE on proteomic changes in both the skeletal muscle and the epididymal fat pad (EFP) of high-fat-diet-induced obese mice. Bioinformatic analyses were performed on differentially regulated proteins using gene ontology enrichment analysis and ingenuity pathway analysis. Eight weeks of AE significantly reduced body weight, increased the serum FNDC5 level, and improved the homeostatic model assessment of insulin resistance. A high-fat diet caused alterations in a subset of proteins involved in the sirtuin signaling pathway and the production of reactive oxygen species in both skeletal muscle and EFP, leading to insulin resistance, mitochondrial dysfunction, and inflammation. On the other hand, AE upregulated skeletal muscle proteins (NDUFB5, NDUFS2, NDUFS7, ETFD, FRDA, and MKNK1) that enhance mitochondrial function and insulin sensitivity. Additionally, the upregulation of LDHC and PRKACA and the downregulation of CTBP1 in EFP can promote the browning of white adipose tissue with the involvement of FNDC5/irisin in the canonical pathway. Our study provides insights into AE-induced molecular responses and may help further develop exercise-mimicking therapeutic targets.

Aerobic Exercise Modulates Proteomic Profiles in Gastrocnemius Muscle of db/db Mice, Ameliorating Sarcopenia

“…Most proteomics research has been designed with respect to and conducted on skeletal muscles to investigate the impact of aerobic exercise on wild-type (C57BLKS/J) and high-fat-diet (HFD)-adherent mice compared to sedentary controls [ 8 , 9 , 10 ]. These HFD mice show increased obesity and insulin action impairment, much like db/db mice.…”

“…The smaller section of gastrocnemius and soleus muscle from the SED and ET groups were fixed with formalin (10%) and embedded in paraffin, as previously described [ 10 ]. Thin tissue slices (4 µm) of the sections stained with hematoxylin and eosin (H & E) were digitalized using a Imager Z2 microscope (Carl Zeiss Microimaging, Göttingen, Germany) and TissueFAXS viewer-version: 7.1.6245.139 software (TissueFAXS Plus Scanning System, TissueGnostics, Vienna, Austria).…”

“…According to our literature review, substantial impacts of physical activity on both mouse (C57BLKS/J) and human skeletal muscles have been extensively investigated under healthy conditions [ 7 , 8 , 9 , 10 ]. Alterations in metabolic pathways and tissue regeneration were remarkable in exercise groups compared to controls.…”

The Participation of Irisin in the Mechanisms of Weight Loss in Obesity

“…The effect of the combined intervention was the strongest [17]. In another study, eight weeks of aerobic exercise in mice significantly lost body weight, increased serum FNDC5 levels, and improved assessment of a homeostatic model of insulin resistance [18].…”

“…Вплив комбінованої інтервенції був найсильнішим [17]. В іншій роботі вісім тижнів аеробних навантажень у мишей значно знизили масу тіла, підвищили рівень FNDC5 у сироватці крові та покращили оцінку гомеостатичної моделі резистентності до інсуліну [18].…”