The role of CD36-Fabp4-PPARγ in skeletal muscle involves insulin resistance in intrauterine growth retardation mice with catch-up growth

Background Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. Methods The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. Results After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). Conclusions LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways.

Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models

Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12 weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline.

Neuronal mechanisms of ginseng on antiobesity effects: implication of its synergistic benefits with physical exercise

Obesity is a chronic disease of increasing prevalence in most countries, which leads to substantial increase in morbidity, and mortality in association with diabetes, hyperlipidaemia, hypertension, and other cardiovascular diseases. Many factors have been attributed to an epidemic of obesity including sedentary lifestyle, high-fat diets (HFD), and consumption of large amount of modern fast foods. Panax ginseng C. A. Meyer (PG) has several pharmacological and physiological effects. In particular, PG and saponin fractions from PG show a variety of efficacies such as antifatigue, hyperlipidemia, hypertension and noninsulin-dependent diabetes mellitus and obesity. We have revealed that ginseng and ginsenosides can decrease food intake energy expenditure by stimulating appetite regulatory hormones and can reduce energy intake. Exercise/physical activity is well known as modality for treating the disease of overweight and obesity. It is suggested that natural products and their combinations with exercise may produce a synergistic activity that increases their bioavailability and action on multiple molecular targets, offering advantages over chemical treatments. This review is aimed at evaluating the antiobesity efficacy of ginseng and ginsenosides and delineating the mechanisms by which they function. Finally, we review information regarding interactions between ginseng and physical exercise in protecting against weight gain and obesity.

Curcumin exerts a protective effect against obesity and liver injury induced by an atherogenic diet

Background: Curcumin (Cur) is a natural yellow polyphenol extracted from the turmeric rhizome (Curcuma longa). Cur is known for its potential therapeutic properties as an analgesic, anti-inflammatory, antioxidant, antimicrobial, hepatoprotective, and anti-mutagenic, although some of these biological activities remain unproven. Epidemiological studies have shown a positive relationship between high-fat diets and diet-related chronic diseases. We hypothesized that some adverse effects of consuming atherogenic or high-fat diets (AD) can be ameliorated by Cur supplementation. Using an experimental model of rats, this study investigated the significance of Cur when it is given as a supplement in an AD.Methods: Healthy adult Wistar rats were randomly assigned to one of three groups. Controls (C) received a standard diet and experimental rats were fed with AD or AD+Cur for 5 weeks. Cur (100 mg/kg body weight) was given orally daily, plus piperine (5 mg/kg body weight). The effect of Cur supplementation was studied on zoometrics, visceral fat content, serum lipids profile, hepatosteatosis, liver function and oxidative status. Results: Diets did not alter energy consumption. As compared to the other groups, AD+Cur group showed a lower total visceral fat content, percentage of perirenal, mesenteric, and pelvic fat, and body weight gain (P< 0.05). Serum total cholesterol (P<0.0001), non-HDL-C (P<0.0001) levels were significantly higher in AD groups as compared with C. Serum triglycerides and HDL-C levels remained similar among groups (P>0.05). AD induced a liver injury with macrovesicular steatosis and portal inflammation. AD+Cur rats presented microvesicular steatosis with no inflammation, achieving the lowest level of alanine aminotransferase (ALT; P<0.0001) and reductions of aspartate aminotransferase (AST; P<0.0001). Liver homogenates from AD+Cur showed that Cur supplementation reduced the dichlorofluorescein diacetate (DCFH-DA) oxidation rate induced by AD by 25 % and deferoxamine and superoxide dismutase inhibited DCFH-DA. Conclusion: Cur as a dietary supplement showed a protective effect against obesity and inflammation, but its cardioprotective ability remained unproved. Cur may develop as a promising therapeutic agent for liver diseases induced by oxidative stress. This study provides supporting evidence to confirm the beneficial effects of curcumin from the point of view of functional food science. Keywords: curcumin, liver injury, ROS, atherogenic diet, visceral fat, obesity

Soluble Epoxide Hydrolase Deletion Limits High-Fat Diet-Induced Inflammation

The soluble epoxide hydrolase (sEH) enzyme is a major regulator of bioactive lipids. The enzyme is highly expressed in liver and kidney and modulates levels of endogenous epoxy-fatty acids, which have pleiotropic biological effects including limiting inflammation, neuroinflammation, and hypertension. It has been hypothesized that inhibiting sEH has beneficial effects on limiting obesity and metabolic disease as well. There is a body of literature published on these effects, but typically only male subjects have been included. Here, we investigate the role of sEH in both male and female mice and use a global sEH knockout mouse model to compare the effects of diet and diet-induced obesity. The results demonstrate that sEH activity in the liver is modulated by high-fat diets more in male than in female mice. In addition, we characterized the sEH activity in high fat content tissues and demonstrated the influence of diet on levels of bioactive epoxy-fatty acids. The sEH KO animals had generally increased epoxy-fatty acids compared to wild-type mice but gained less body weight on higher-fat diets. Generally, proinflammatory prostaglandins and triglycerides were also lower in livers of sEH KO mice fed HFD. Thus, sEH activity, prostaglandins, and triglycerides increase in male mice on high-fat diet but are all limited by sEH ablation. Additionally, these changes also occur in female mice though at a different magnitude and are also improved by knockout of the sEH enzyme.

Ketogenic Diet for Obese COVID-19 Patients: Is Respiratory Disease a Contraindication? A Narrative Review of the Literature on Ketogenic Diet and Respiratory Function

Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.

Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction. To compare the efficacy of low-carbohydrate diets (LCDs) with low-fat diets (LFDs) in body weight and glycemic control for type 2 diabetes mellitus (T2DM) patients, and their cardiovascular and renal safety. Methods. We searched PubMed, Ovid, Embase databases, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April, 2021. Randomized controlled trials (RCTs) which lasted more than 3 months were included. The primary outcomes are the mean change from baseline in glycated haemoglobin (HbA1c) and body weight loss. Secondary outcomes included mean difference in lipid parameters, blood pressures, and serum creatinine. Results. Totally, 12 RCTs met inclusion criteria representing 761 patients. Compared with LFDs, treatment with LCDs achieved significant reduced HbA1c by 0.35% (95% CI: −0.45, −0.24; P < 0.00001). LCDs appeared to be more beneficial in decreasing body weight than LFDs (WMD = −2.99 kg; 95% CI: −4.36, −1.63; P < 0.0001), especially in the subgroup that used VLCDs (WMD = −9.49 kg; 95% CI: −12.88, −6.09, P < 0.00001). For cardiovascular risk factors, the LCD interventions significantly reduced TG concentration (WMD: −0.20 mmol/l; 95% CI: −0.31, −0.10; P = 0.0001) and increased HDL-C concentration (WMD: 0.09 mmol/l; 95% CI: 0.05,0.13; P < 0.00001). Subgroup analyses demonstrated that the difference in HbA1c, TG, and HDL-C between two dietary restrictions respectively lasted up to 1.5 and 2 years, whereas the beneficial effects of body weight loss diminished over time and disappeared after 2 years. LCDs were not associated with decreased level of TC or LDL-C, neither SBP nor DBP in comparison with LFDs. Moreover, no significant difference in serum creatinine could be found among such two diet interventions. Conclusions. LCDs are superior to LFDs for T2DM patients in improving HbA1c and reducing body weight, with a rewarding effect of some cardiovascular risk factors in a longer-term diabetes management. However, available data are insufficient to evaluate the association between diet interventions and renal safety. Future larger longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of LCDs compared with LFDs.