Background:
In humans and mice, obesity is associated with chronic low-grade inflammation and fibrosis in adipose tissue that is reduced by caloric restriction, but the effects of intermittent fasting (IF) are unclear.
Methods:
Ten-week old male C57BL/6J mice were fed a lard based high-fat (HFD; 43% fat) or chow (18% fat) diet for 8wks ad-libitum (AL). Mice on each diet were then randomised to AL or IF for 8wks (n=8/group). Intermittent 24h fasts were initiated at Z11 for 3 non-consecutive days/week, with AL access on non-fast days. Body weight and energy intake were measured daily. Oral glucose tolerance (2g/kg body weight) was assessed prior to sacrifice. In gonadal fat, markers of inflammation (F4/80, Mac2, CD11c, Nos2, Arg1, Erg2, Ccl2 and Ccl3) and extracellular matrix (Col3a1, Col6a1, Mmp2, Mmp9 and Timp1) were examined by qPCR. Ucp1 mRNA and protein (by immunohistochemistry) in gonadal and inguinal fat were assessed.
Results:
Energy intake was similar between chow groups, but was 26% lower in HFD-IF than HFD-AL group. Final body weight, gonadal and inguinal fat mass was increased in AL vs. IF groups (P<0.05). Glucose tolerance was impaired in HFD-AL group, and improved by IF, with a greater improvement in chow-IF vs. HFD-IF (all P<0.05). Fasting insulin was increased by HFD-AL, and decreased in HFD-IF vs. HFD-AL only (all P<0.001). IF reduced Mac2, CD11c, Nos2, Arg1, Erg2, CCL2, Col6a1 and Timp1 expression, and increased MMP2/TIMP1 and MMP9/TIMP1 vs. AL (all P<0.05). IF increased Ucp1 gene expression in both gonadal and inguinal fat and Ucp1 immunostaining in inguinal fat (P<0.05).
Conclusions:
Intermittent fasting decreases energy intake, fat mass, and markers of adipose tissue inflammation and fibrosis, and improves glucose tolerance. IF may promote adipose tissue browning in lean and diet-induced obese mice.