FIGURE 6.

Muscle Bmal1 ablation reduces circulating lipid levels and hepatic accumulation. A, The impact of muscle Bmal1 deficiency on systemic lipids levels, including free fatty acid (FAA), glycerol, triglyceride, and cholesterol in mBMCtr (n = 8) and mBMKO mice (n = 10) under fasted or refed conditions. B and C, Representative images of gross appearance (B), and oil-red-O staining (C) of mBMCtr and mBMKO mice after 16 hour overnight fasting. D, Hepatic triglyceride content analysis of mBMCtr (n = 6) and mBMKO mice (n = 8) during fasting and refeeding. E and F, Hepatic triglyceride content at ZT2 and ZT10 under normal chow (E), or after high-fat diet for 10 weeks (F), in mBMCtr (n = 7) and mBMKO mice (n = 6), with representative images of oil-red-O staining at ZT2 (G). H, Proposed working model of skeletal muscle Bmal1-driven clock in the regulation of glucose and lipid homeostasis. Bmal1 is induced by feeding-associated insulin stimulation. Loss of Bmal1 in myocytes impairs response to feeding with reduced glucose utilization and induction of fat oxidation. Altered metabolic oxidation in the Bmal1-deficient muscle significantly attenuates global glucose disposal but depletes circulating lipids and its hepatic storage