Thermogenesis-independent metabolic benefits conferred by isocaloric intermittent fasting in ob/ob mice

Abstract

Intermittent fasting (IF) is an effective dietary intervention to counteract obesity-associated metabolic abnormalities. Previously, we and others have highlighted white adipose tissue (WAT) browning as the main underlying mechanism of IF-mediated metabolic benefits. However, whether IF retains its efficacy in different models, such as genetically obese/diabetic animals, is unknown. Here, leptin-deficient ob/ob mice were subjected to 16 weeks of isocaloric IF, and comprehensive metabolic phenotyping was conducted to assess the metabolic effects of IF. Unlike our previous study, isocaloric IF-subjected ob/ob animals failed to exhibit reduced body weight gain, lower fat mass, or decreased liver lipid accumulation. Moreover, isocaloric IF did not result in increased thermogenesis nor induce WAT browning in ob/ob mice. These findings indicate that isocaloric IF may not be an effective approach for regulating body weight in ob/ob animals, posing the possible limitations of IF to treat obesity. However, despite the lack of improvement in insulin sensitivity, isocaloric IF-subjected ob/ob animals displayed improved glucose tolerance as well as higher postprandial insulin level, with elevated incretin expression, suggesting that isocaloric IF is effective in improving nutrient-stimulated insulin secretion. Together, this study uncovers the insulinotropic effect of isocaloric IF, independent of adipose thermogenesis, which is potentially complementary for the treatment of type 2 diabetes.

Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity

“…The WAT of mice with antibiotic-induced microbiome depletion exhibits a browning phenotype, and microbiota depletion promotes eosinophil infiltration, type 2 cytokine activation and M2 macrophage polarization, which results in beige cell reconstruction 10 . Intermittent fasting-induced alteration in the gut microbiota can stimulate the expression of monocarboxylate transporter 1 in beige cells of DIO mice 11 but has negative effects on thermogenesis in genetically (ob/ob) obese mice 12 . Leptin, as a secretory protein of adipocytes, is a mediator in the regulation of energy intake and consumption and can increase BAT thermogenesis via its action on the hypothalamus 13 , as well as enhance the browning of WAT by activating the Janus-activated kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway 14 or inducing the STAT3-PRDM 16 complex 15 .…”

Diet and Lifestyle Guidelines and Desirable Levels of Risk Factors and Protective Factors for Prevention of Dementia: A Scientific State-Ment From Joint Symposium of Jaas and Apcns

“…Intermittent fasting with isocaloric diet showed no effects on thermogenesis nor induce browning of white adipose tissue in ob/ob mice. Despite the lack of improvement in insulin sensitivity, isocaloric diet on intermittent fasting, in ob./ob animals resulted in improvement in glucose tolerance as well as higher postprandial insulin level, with elevated incretin expression, indicating that intermittent fasting with isocaloric diet is effective in improving nutrient-stimulated release of insulin which complimentary for all the CMDs [75]. During the process of ageing, there is accumulation of dysfunctional and damaged cellular proteins and organelles, resulting in a disruption of cellular homeostasis and progressive degeneration which increases the risk of cell death.…”

“…These markers should be targeted by modification of behavioural risk factors for prevention of dementia. Epidemiological studies indicate that apart from sedentary behavior and diet, different behaviors such as eating habits, eating and sleeping late at night, depression, type-A behavior, insomnia, night shift work and circadian disruption of sleep, have been reported to predispose to CVDs, T2DM and other NCDs [23][24][25][26][27][28][29][71][72][73][74][75]. Therefore, behavioral modulations appear to be most important factors in the pathogenesis and prevention of cardio-metabolic diseases (CMDs) because it may also inhibit dementia.…”

“…Intermittent fasting appears to be an effective dietary intervention to counteract the associated metabolic abnormalities with CMD [75]. It has been proposed that browning of white adipose tissue (WAT) is the main underlying mechanism for the occurrence of fasting -mediated metabolic benefits.…”

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

“…Intermittent fasting (IF) is an effective weight control strategy, but its mechanism is still unclear. A new study demonstrated that isocaloric IF improves glucose tolerance and postprandial insulin levels, and increases incretin expression in leptin-deficient ob/ob mice, indicating that isocaloric IF is effective in ameliorating nutrient-stimulated insulin secretion [ 73 ]. It has been found that IF can selectively stimulate the development of beige adipocytes in WAT, and significantly improve obesity, insulin resistance and liver steatosis by regulating intestinal microbial composition to increase the biosynthesis of acetate and lactate [ 74 ].…”