Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling. Yang Wanwei,Cao Meng,Mao Xiaodong,Wei Xiao,Li Xingjia,Chen Guofang,Zhang Jiaming,Wang Zhiguo,Shi Jianfeng,Huang HouCai,Yao Xiaoming,Liu Chao Nutrition research (New York, N.Y.) Because of unhealthy lifestyles, a large number of people are suffering from hepatic lipid accumulation and nonalcoholic steatohepatitis. Energy restriction (ER) is an effective nutritional intervention for preventing chronic disease. However, poor compliance with continuous ER limits its effectiveness. As an alternative to daily ER, alternate-day fasting (ADF) may be more effective. We hypothesized that ADF would improve obesity, hyperglycemia, and insulin resistance and protect the liver against high-fat diet (HFD)-induced steatosis and inflammation. In this study, we used C57BL/6 mice to test the beneficial effects of ADF. Thirty male 6-week-old C57BL/6 mice were divided into 3 groups (10 per group, total N = 30): 1 group was fed chow diet, the second was fed HFD ad libitum, and the third group was submitted to ADF. The mice in the third group were fed the HFD ad libitum every other day and fasted the following day. After 12 months, the mice submitted to ADF exhibited reduced body weights and fasting glucose levels and improved insulin resistance and hepatic steatosis compared with continuous HFD-fed mice. In addition, the serum transaminase levels in the mice of the ADF group were lower than those of the HFD group. Moreover, the ADF regimen suppressed the expression levels of Toll-like receptor 4 and nuclear factor κB protein in the liver and suppressed the inflammatory pathway genes interleukin 1β, tumor necrosis factor α, and serum amyloid A. These finding indicate that long-term ADF protects mouse livers against HFD-induced hepatic steatosis and hepatocellular damage associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling. 10.1016/j.nutres.2016.02.001

Short-term moderate caloric restriction in a high-fat diet alleviates obesity via AMPK/SIRT1 signaling in white adipocytes and liver. Food & nutrition research Background:Obesity is a growing problem for public health worldwide. Calorie restriction (CR) is a safety and effective life intervention to defend against obesity. Short-term moderate CR may be a more favorable strategy against this pathology. However, the mechanisms behind the effects of CR remain to be clarified. Increased energy expenditure in the liver and brown adipose tissue could potentially be manipulated to modulate and improve metabolism in obesity. Moreover, nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) are well-characterized metabolic modulators. We aim to explore the anti-obesity effects of short-term moderate CR by improving energy metabolism via the SIRT1/AMPK pathway in white adipocytes and liver in a mouse model of obesity. Methods:Male C57BL/6 mice were randomized into two groups receiving either a standard or a high-fat diet (HFD) for 8 weeks to induce obesity. The HFD-induced obese mice were further randomized into two groups: HFD group or CR group (received 75% of the food eaten by HFD group). Their energy metabolism, white adipose tissue (WAT) contents, hepatic fat deposition, the expression of AMPK, SIRT1, peroxisome proliferators γ-activated receptor coactivator-1α (PGC-1α), nuclear factor kappa B (NF-κB), endothelial nitric oxide synthase (eNOS) in WAT, and hepatic tissues were determined. Results:After 4 weeks, body weight, total serum cholesterol, fasting blood glucose, and insulin levels were significantly lower in the CR group. Moreover, CR ameliorated hepatocyte steatosis, attenuated white adipogenesis, and increased energy expenditure and expressions of SIRT1, PGC-1α, and phosphorylated AMPK in subcutaneous WAT and the hepatic tissues. In addition, CR reduced the protein levels of NF-κB and increased the eNOS expression. Conclusion:Short-term moderate CR decreases obesity, increases the thermogenesis, and inhibits inflammation in a mouse model of obesity, probably via the activation of the AMPK/SIRT1 pathway in WAT and liver. 10.29219/fnr.v66.7909

Long-term remission of type 2 diabetes after very-low-calorie restriction and related predictors. Frontiers in endocrinology Purpose:Very low-calorie restriction (VLCR) can induce remission of type 2 diabetes mellitus (T2DM), but its long-term remission and related predictors have not been clarified. The aim of present study is to investigate the effect of VLCR in inducing long-term T2DM remission, and the underlying predictors. Methods:A total of 61 participants with T2DM who received 9 days of VLCR from Dec 2012 to Oct 2020 were followed up in Nov 2021, and divided into responders and non-responders groups. Responders were defined as HbA1c < 6.5% over at least 3 months in the absence of pharmacotherapy. Clinical characteristics were compared between responders and non-responders. Potential predictors were examined by logistic regression analyses based on clinical data before and after VLCR. Results:Forty-four participants were successfully followed up, including 19 males and 25 females. Long-term remission was observed in 17 participants (38.64%) after VLCR, with a median 7.83 years. Compared with non-responders, responders had a shorter disease duration, a lower fasting blood glucose (FBG) level, a higher fasting insulin level, and better HOMA-β after VLCR. Besides, acute insulin response (AIR), insulin area under curve in intravenous and oral glucose tolerance test (IVGTT-IAUC and OGTT-IAUC) in responders were higher than those in non-responders after VLCR. Multivariable logistic analysis showed that higher post-VLCR IVGTT-IAUC predicted a longer T2DM remission. Conclusions:After VLCR, more than one third of the participants presented remission over up to 8 years. The improvement of β-cell function, especially the restoration of first-phase insulin-secreting capacity, could prolongate the remission. 10.3389/fendo.2022.968239

Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients. Guo Yi,Luo Shiyun,Ye Yongxin,Yin Songping,Fan Jiahua,Xia Min The Journal of clinical endocrinology and metabolism CONTEXT:Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. OBJECTIVE:The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). DESIGN AND SETTING:A randomized clinical trial was conducted at a community health service center. PATIENTS:Participants included adults with MS, age 30 to 50 years. INTERVENTION:Intervention consisted of 8 weeks of "2-day" modified IF. MAIN OUTCOME MEASURE:Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. RESULTS:Thirty-nine patients with MS were included: 21 in the IF group and 18 in the control group. On fasting days, participants in the IF group reduced 69% of their calorie intake compared to nonfasting days. The 8-week IF significantly reduced fat mass, ameliorated oxidative stress, modulated inflammatory cytokines, and improved vasodilatory parameters. Furthermore, IF induced significant changes in gut microbiota communities, increased the production of short-chain fatty acids, and decreased the circulating levels of lipopolysaccharides. The gut microbiota alteration attributed to the IF was significantly associated with cardiovascular risk factors and resulted in distinct genetic shifts of carbohydrate metabolism in the gut community. CONCLUSION:IF induces a significant alteration of the gut microbial community and functional pathways in a manner closely associated with the mitigation of cardiometabolic risk factors. The study provides potential mechanistic insights into the prevention of adverse outcomes associated with MS. 10.1210/clinem/dgaa644