Caloric restriction following early-life high fat-diet feeding represses skeletal muscle TNF in male rats

Chronic metabolic diseases are on the rise worldwide and their etiology is multifactorial. Among them, inflammatory components like Tumor Necrosis Factor (TNF), contribute to whole-body impairment. Caloric Restriction (CR) combats diseases, but how it reduces inflammation remains understudied. We aimed evaluate impact of chronic CR muscle inflammation, in particular TNF. In our study, 4-week old male Sprague-Dawley rats were fed a high-fat diet (HF, 45% Kcal fat from lard) ad libitum for 3 months. After estimation energy requirement (1 month), they then divided into three groups: HF (OL), weight maintenance with AIN93M (9.5% fat; ML, 100% requirement), caloric restriction (CR, 75% requirement). This dietary intervention continued six At this point, sacrificed gastrocnemius was collected. induced profound shift lean mass, decreased growth factor IGF-1. Muscle qPCR analysis showed marked decrease TNF (premRNA, mRNA, protein) by CR, accompanied Tnf promoter DNA hypermethylation. increased expression histone deacetylase Sirt6 methyltransferase Suv39h1, together coding region binding NF- κB C/EBP-β. Following miRNA database mining, revealed that downregulated proinflammatory miR-19b anti-inflammatory miR-181a its known targets. able regulate muscle-specific targeting NF-κB pathway as well transcriptional post-transcriptional regulation gene.