Effects of a high-fat diet and cage restriction-induced physical inactivity in youth on autophagy in rat skeletal muscle

Abstract

This study aimed to elucidate the effects of long-term high-fat diet (HFD) consumption and cage restriction-induced physical inactivity (IN) during youth on skeletal muscle autophagy in rats. Three-week-old male Wistar rats were randomly assigned to two dietary groups: the normal diet (ND) and HFD groups. Each group was further subdivided into control (CON) and IN conditions, resulting in four experimental groups (n = 7-8). The HFD group was provided with a diet containing approximately 60% of total calories from crude fat for 16 weeks, from 4 to 20 weeks of age. The ND group received a standard diet for the same duration. The physical inactivity intervention during youth involved restricting the rats’ range of activity by housing them in smaller cages for eight weeks. After 12 weeks of age, the behavioral restrictions were lifted, and all groups of rats were housed in normal-sized cages for eight weeks. The ‘diet group’ and ‘condition’ factors exerted significant effects on the relative muscle weight of the gastrocnemius muscle. The HFD groups exhibited a notable decline in relative muscle weight compared to their ND counterparts. While no significant alterations were observed in LC3-II or p62 expression levels, the ‘diet group’ factor significantly influenced LC3-II/I levels in the white gastrocnemius muscle. These levels were markedly reduced in the HFD group. Our findings suggest that 16 weeks of HFD consumption leads to a reduction in autophagy flux, specifically within the white portion of the gastrocnemius muscle, but this effect is not influenced by cage restriction-induced physical inactivity during youth.