Background: Fasting activates autophagy in peripheral tissues, and blocking autophagy increases hepatosteatosis and alters glucose metabolism in mouse liver (1). This study examined whether intermittent fasting activates autophagy pathways in mouse quadriceps and human vastus lateralis muscle.
Methods: Women (n=31,51±2y, BMI31.8±4.3kg/m2) were randomized to 1 of 2 groups for 8-weeks, and provided with foods at 70%(IF70) or 100%(IF100) of energy requirements. Participants fasted for 24h from 0800h, 3 days/week. Samples were collected at baseline (12h overnight fast) and twice at Week 8 (12h and 24h fast). Ten week old C57BL/6J male mice were fed high-fat diet (HFD) (42% energy from fat) or chow for 8 weeks, before randomisation to AL or IF (24h fasts initiated at ZT11 on 3 non-consecutive days/week) for a further 8 weeks (8-16/group). Mice were sacrificed in fed state (AL, IF-FED) and after 24h of fasting (IF-FAST). Autophagy related genes MAPLC3B, BECN1, TFEB, SQSTM and LAMP were assessed by qPCR and SQSTM1 protein by western blot.
Results: In humans, greater weight and fat loss, and reductions in glucose and insulin were observed in IF70 vs IF100 groups (all P<0.01). Increased SQSTM mRNA level in muscle was observed in the IF70 group following an overnight fast (P=0.05). In mice, IF reduced body weight in high fat diet only, whereas gonadal and inguinal fat pad weight were reduced by IF in both diet groups (all P<0.05). SQSTM mRNA levels in quadriceps were lower in HFD-AL vs chow AL mice (P<0.001) and were increased by IF in IF-FAST vs AL and IF-FED mice that were fed high fat diet (P<0.001). MAPLC3B, BECN1 and TFEB mRNA levels in and SQSTM protein level in muscle were unchanged.
Conclusion: IF increased SQSTM mRNA levels in mice and humans who were in overall energy deficit but not when in overall energy balance.