Hepatoprotective Effect of Herb Formula KIOM2012H against Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a hepatic ailment with a rapidly increasing incidence due to dietary hypernutrition and subsequent obesity. Fatty liver disease can lead to steatohepatitis, fibrosis, cirrhosis, and even cancer, which is associated with various complications. Discovering effective natural materials and herbs can provide alternative and complementary medical treatments to current chemical pharmaceuticals. To develop an effective natural agent for NAFLD, we formulated a combination of four herb mixtures (KIOM2012H) and observed lipid-lowering efficacy. The inhibitory effects of KIOM2012H on free fatty acid-induced lipid accumulation, triglyceride contents, and gene expressions were analyzed in HepG2 cells. Using high fat diet-fed mice, body weight changes, gross liver appearances, hepatic triglyceride contents, and gene expressions were evaluated. KIOM2012H dose-dependently inhibited lipid accumulation and gene expressions involved in lipogenesis and related regulators. Experimental animals also showed a decrease in body weight changes and lipid-associated physiological parameters. This study shows that KIOM2012H has an alleviating effect on fatty acid and lipid accumulation, and therefore can be applied for development of new therapeutic pharmaceuticals for treatment of NAFLD using natural products and herbs.     

Effects of Lingonberry (Vaccinium vitis-idaea L.) Supplementation on Hepatic Gene Expression in High-Fat Diet Fed Mice

The prevalence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide in association with Western-style diet and increasing obesity. Lingonberry (Vaccinium vitis-idaea L.) is rich in polyphenols and has been shown to attenuate adverse metabolic changes in obese liver. This paper investigated the effects of lingonberry supplementation on hepatic gene expression in high-fat diet induced obesity in a mouse model. C57BL/6N male mice were fed for six weeks with either a high-fat (HF) or low-fat (LF) diet (46% and 10% energy from fat, respectively) or HF diet supplemented with air-dried lingonberry powder (HF + LGB). HF diet induced a major phenotypic change in the liver, predominantly affecting genes involved in inflammation and in glucose and lipid metabolism. Lingonberry supplementation prevented the effect of HF diet on an array of genes (in total on 263 genes) associated particularly with lipid or glucose metabolic process (such as Mogat1, Plin4, Igfbp2), inflammatory/immune response or cell migration (such as Lcn2, Saa1, Saa2, Cxcl14, Gcp1, S100a10) and cell cycle regulation (such as Cdkn1a, Tubb2a, Tubb6). The present results suggest that lingonberry supplementation prevents HF diet-induced adverse changes in the liver that are known to predispose the development of NAFLD and its comorbidities. The findings encourage carrying out human intervention trials to confirm the results, with the aim of recommending the use of lingonberries as a part of healthy diet against obesity and its hepatic and metabolic comorbidities.     

Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.     

学龄期儿童肥胖相关性脂肪肝及血脂代谢异常对照研究

目的 探讨兰州市学龄期儿童肥胖非酒精性脂肪肝(nonalcoholic fatty liver disease, NAFLD)、血脂代谢异常及其相关因素。方法 2011年6-10月选取3所小学1至6年级7~14岁小学生作为研究对象。选取年龄、性别匹配体质指数(body mass index, BMI)正常儿童作为对照。行腹部B超、采空腹静脉血5 mL进行实验室检查, 包括天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、谷氨酰转肽酶(gamma glutamyl transpeptidase, GGT)、总胆固醇(total cholesterol, CHOL)、甘油三酯(triglyceride, TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)。结果 筛查出肥胖儿童80例, 与51例正常对照儿童比较, 肥胖组儿童的AST、ALT、GGT、CHOL、TG、LDL-C增高, HDL-C减低, 差异有统计学意义(P<0.05)。AST、ALT、GGT、TG、LDL-C与NAFLD发病呈正相关且为危险因素;HDL-C呈负相关为保护因素。肥胖儿童NAFLD检出率为27.5%(22/80);对照组未检出NAFLD, 肥胖儿童的NAFLD发生率明显高于正常儿童(P<0.05)。肥胖伴有NAFLD组较肥胖不伴NAFLD组AST、ALT、GGT、TG升高, HDL-C降低;差异具有统计学意义(P<0.05)。结论 肥胖导致学龄期儿童的肝功能损害、血脂代谢异常甚至可造成非酒精性脂肪肝的发生;非酒精性脂肪肝更进一步加重了肝功能损害及血脂代谢紊乱。     

Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver.     

The Marine Microalga,Tisochrysis lutea,Protects against Metabolic Disorders Associated with Metabolic Syndrome and Obesity

Long-chain polyunsaturated fatty acids n-3 series and especially docosahexaenoic acid are known to exert preventive effects on metabolic disturbances associated with obesity and decrease cardiovascular disease risk. n-3 LC-PUFAs are mainly consumed in the form of fish oil, while other sources, such as certain microalgae, may contain a high content of these fatty acids. The aim of this study was to evaluate the effects of Tisochrysis lutea (Tiso), a microalga rich in DHA, on metabolic disorders associated with obesity. Three male Wistar rat groups were submitted for eight weeks to a standard diet or high-fat and high fructose diet (HF), supplemented or not with 12% of T. lutea (HF-Tiso). The supplementation did not affect plasma alanine aminotransferase (ALAT). Bodyweight, glycemia and insulinemia decreased in HF-Tiso rats (ANOVA, p < 0.001), while total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C) increased (ANOVA, p < 0.001) without change of low-density lipoprotein-cholesterol (LDL-C) and triacylglycerol (TAG) levels. Tiso supplementation decreased fat mass and leptinemia as well as liver TAG, cholesterol and plasma tumor necrosis factor-alpha levels (ANOVA, p < 0.001) while it did not affect interleukin 6 (IL-6), IL-4 and lipopolysaccharides levels. HF-Tiso rats showed an increase of IL-10 level in abdominal adipose tissue (ANOVA, p < 0.001). In conclusion, these results indicated that DHA-rich T. lutea might be beneficial for the prevention of obesity and improvement of lipid and glucose metabolism.     

Bifidobacterium animalis ssp. lactis MG741 Reduces Body Weight and Ameliorates Nonalcoholic Fatty Liver Disease via Improving the Gut Permeability and Amelioration of Inflammatory Cytokines

Diet-induced obesity is one of the major causes of the development of metabolic disorders such as insulin resistance and nonalcoholic fatty liver disease (NAFLD). Recently, specific probiotic strains have been found to improve the symptoms of NAFLD. We examined the effects of Bifidobacterium animalis ssp. lactis MG741 (MG741) on NAFLD and weight gain, using a mouse model of high-fat-diet (HFD)-induced obesity. HFD-fed mice were supplemented daily with MG741. After 12 weeks, MG741-administered mice exhibited reduced fat deposition, and serum metabolic alterations, including fasting hyperinsulinemia, were modulated. In addition, MG741 regulated Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SREBP-1), and carbohydrate-responsive element-binding protein (ChREBP) expression and lipid accumulation in the liver, thereby reducing the hepatic steatosis score. To determine whether the effects of MG741 were related to improvements in gut health, MG741 improved the HFD-induced deterioration in gut permeability by reducing toxic substances and inflammatory cytokine expression, and upregulating tight junctions. These results collectively demonstrate that the oral administration of MG741 could prevent NAFLD and obesity, thereby improving metabolic health.     

Hepatic Steatosis as a Marker of Metabolic Dysfunction

Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds hepatic fatty acid disposal by oxidation and triglyceride export. Hepatic steatosis is therefore the biochemical result of an imbalance between complex pathways of lipid metabolism, and is associated with an array of adverse changes in glucose, fatty acid, and lipoprotein metabolism across all tissues of the body. Intrahepatic triglyceride (IHTG) content is therefore a very good marker (and in some cases may be the cause) of the presence and the degree of multiple-organ metabolic dysfunction. These metabolic abnormalities are likely responsible for many cardiometabolic risk factors associated with NAFLD, such as insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal.     

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate,High Fat Diet-Fed Rats

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.     

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood

Nicotinamide riboside, an NAD⁺ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD⁺ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.     

Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters.     

维生素D治疗肥胖合并非酒精性脂肪肝儿童的临床研究

目的 分析肥胖合并非酒精性脂肪肝(NAFLD)儿童血清25羟维生素D[25(OH)D]水平以及补充维生素D(VD)对NAFLD的疗效,为VD用于儿童NAFLD治疗提供临床依据。方法 1)2020年1月—2021年8月,纳入102名6～14周岁的肥胖儿童,依据肝脏超声分为肥胖合并NAFLD组和肥胖无NAFLD组;并纳入健康体检儿童作为对照组。比较3组儿童血清25(OH)D、血脂、转氨酶及胰岛素抵抗指数(HOMA-IR)等指标的差异。2)将58名肥胖合并NAFLD患儿随机分为：VD干预组和VD非干预组。两组儿童均予以饮食运动指导,VD干预组在此基础上补充骨化三醇800 U/d,共16周。检测并比较两组儿童干预前后各项指标的变化。结果 1)肥胖合并NAFLD组血清25(OH)D水平[(20.94±6.88) ng/ml]显著低于肥胖无NAFLD组[(24.31±7.69) ng/ml,P<0.05]及健康对照组[(29.19±5.44) ng/ml,P<0.01]。且血清25(OH)D水平与BMI及HOMA-IR呈负相关(r=-0.37、-0.71,P<0.01)。2)肥胖...     

Effects of Phytosterol Supplementation on Serum Levels of Lipid Profiles,Liver Enzymes,Inflammatory Markers,Adiponectin, and Leptin in Patients Affected by Nonalcoholic Fatty Liver Disease: A Double-Blind,Placebo-Controlled,Randomized Clinical Trial

ABSTRACT

Objective: Considering the high prevalence of nonalcoholic fatty liver disease and based on the evidence about the role of dietary cholesterol in liver inflammation, and also with regard to the effect of phytosterols on the metabolism of cholesterol, we aimed at exploring the therapeutic potential of phytosterol supplementation against nonalcoholic fatty liver disease.

Method: Thirty-eight patients with nonalcoholic fatty liver disease were randomly divided into two groups: The phytosterol group (n = 19) received a 1.6-g phytosterol supplement daily and the control group (n = 19) received 1.6 g starch daily as placebo for an 8-week period. Blood samples of all patients were taken at baseline (week 0) and at the end of the study (week 8) for measurement of lipid profiles, liver enzymes, inflammatory markers, adiponectin, and leptin.

Results: Phytosterol supplementation significantly improved the levels of low-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, and tumor necrosis factor alpha compared to the placebo group. On the other hand, there were no significant differences between the two groups in total cholesterol, triglycerides, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol, gamma-glutamyl transferase, interleukin 6, high-sensitivity C-reactive protein, adiponectin, and leptin.

Conclusions: The present study suggested that daily consumption of 1.6 g phytosterols efficiently lowers low-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, and tumor necrosis factor alpha in patients with nonalcoholic fatty liver disease.     

The Role of Intestinal Bacteria Overgrowth in Obesity-Related Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO) contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.     

The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice

In this study, we investigated the effects of the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on high-fat-induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. The BW decrease was associated with increased fecal lipids in the high-fat-fed groups (r(2) = 0.521; P < 0.05). EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte chemoattractant protein concentrations in high-fat-fed mice (P < 0.05). EGCG treatment also decreased liver weight, liver triglycerides, and plasma alanine aminotransferase concentrations in high-fat-fed mice (P < 0.05). Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat-induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat-fed control mice (P < 0.05). Our results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat-induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms.     

Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.     

唐山市7～14岁肥胖儿童非酒精性脂肪肝流行现状及危险因素初步分析

目的 初步了解唐山市肥胖儿童非酒精性脂肪肝(NAFLD)流行特点及危险因素,为早期干预提供理论依据。方法 以2018—2019年唐山市学龄儿童体检筛查出的肥胖儿童为研究对象,依年龄分组描述NAFLD患病率,比较NAFLD组与非NAFLD组代谢综合征(MetS)、体重指数(BMI)、腰围(WC)、腰围身高比(WHtR)、转氨酶、尿酸(UA)、糖脂代谢等指标,分析NAFLD发生的危险因素。结果 1)唐山市肥胖儿童NAFLD患病率为34.62%,不同性别间差异无统计学意义(χ²=0.009,P=1.000),NAFLD患病率随年龄增加而增高(r=0.425,P<0.001);2)7～9岁NAFLD组脂代谢紊乱患病率、10～14岁NAFLD脂代谢紊乱、高血压、MetS患病率高于非NAFLD组,差异均有统计学意义(χ²=6.159、10.994、5.543、4.524,P<0.05);3)多因素Logistic回归分析显示NAFLD的危险因素为年龄增长(OR=3.91)、高尿酸血症(OR=2.09)、BMI增加(OR=1.07)、ALT升高(OR=1.04)(P<0.05)。结论 唐山市肥胖儿童总体NAFLD患病率处于较高水平,其患病率随年龄增长而增高;肥胖儿童NAFLD与年龄、高尿酸血症、BMI、ALT水平密切相关。     

Distinct AMPK-Mediated FAS/HSL Pathway Is Implicated in the Alleviating Effect of Nuciferine on Obesity and Hepatic Steatosis in HFD-Fed Mice

Nuciferine (Nuci), the main aporphine alkaloid component in lotus leaf, was reported to reduce lipid accumulation in vitro. Herein we investigated whether Nuci prevents obesity in high fat diet (HFD)-fed mice and the underlying mechanism in liver/HepG2 hepatocytes and epididymal white adipose tissue (eWAT) /adipocytes. Male C57BL/6J mice were fed with HFD supplemented with Nuci (0.10%) for 12 weeks. We found that Nuci significantly reduced body weight and fat mass, improved glycolipid profiles, and enhanced energy expenditure in HFD-fed mice. Nuci also ameliorated hepatic steatosis and decreased the size of adipocytes. Furthermore, Nuci remarkably promoted the phosphorylation of AMPK, suppressed lipogenesis (SREBP1, FAS, ACC), promoted lipolysis (HSL, ATGL), and increased the expressions of adipokines (FGF21, ZAG) in liver and eWAT. Besides, fatty acid oxidation in liver and thermogenesis in eWAT were also activated by Nuci. Similar results were further observed at cellular level, and these beneficial effects of Nuci in cells were abolished by an effective AMPK inhibitor compound C. In conclusion, Nuci supplementation prevented HFD-induced obesity, attenuated hepatic steatosis, and reduced lipid accumulation in liver/hepatocytes and eWAT/adipocytes through regulating AMPK-mediated FAS/HSL pathway. Our findings provide novel insight into the clinical application of Nuci in treating obesity and related complications.     

The function of the nuclear receptor peroxisome proliferator-activated receptor delta in energy homeostasis

The metabolic function of the nuclear receptor peroxisome proliferator-activated receptor delta (PPAR(delta)) has been established by transfer of the PPAR(delta) gene into adipose tissue of mice in vivo and into adipocytes in culture. Investigators found that PPAR(delta) activation by such transfer leads to up-regulation of energy expenditure by fatty acid oxidation. PPAR(delta) activation also results in lowered serum triglyceride and free fatty acid levels and decreased lipid accumulation. In vivo activation of PPAR(delta) in adipose tissue protects against obesity and fatty liver in mice fed a high-calorie diet. PPAR(delta) also activates the heat-producing uncoupling enzymes in brown adipose tissue (UCP1 and 3) and muscle (UCP2).     

Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a major clinical consequence for people with obesity and metabolic syndrome and is also associated with enteral and parenteral nutrition. Early studies suggested that altered gut microbiota might contribute to obesity by affecting energy harvest from the diet and energy storage in the host. Recent evidence in humans as well as in animal models has linked gut microbiota to the development of NAFLD through the gut‐liver axis. With bacterial overgrowth and increased intestinal permeability observed in patients with NAFLD and in animal models, gut‐derived bacterial products such as endotoxin (lipopolysaccharide) and bacterial DNA are being delivered to the liver through the portal vein and then activate Toll‐like receptors (TLRs), mainly TLR4 and TLR9, and their downstream cytokines and chemokines, leading to the development and progression of NAFLD. Given the limited data in humans, the role of gut microbiota in the pathogenesis of NAFLD is still open to discussion. Prebiotics and probiotics have been attempted to modify the microbiota as preventive or therapeutic strategies on this pathological condition. Their beneficial effects on NALFD have been demonstrated in animal models and limited human studies. However, prospective, appropriately powered, randomized, controlled clinical trials are needed to determine whether prebiotics and probiotics and other integrated strategies to modify intestinal microbiota are efficacious therapeutic modalities to treat NALFD.