Dietary Momordica Cochinchinensis aril ameliorates metabolic dysfunction, nonalcoholic fatty liver, and gut microbiota in diet-induced obese mice

Abstract Background Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis fruit is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic dysfunction and gut microbiota remains unclear. This study was conducted to determine how Momordica cochinchinensis aril (MCA) affects obesity, nonalcoholic fatty liver, insulin resistance and gut microbiota in diet-induced obese mice.Methods Wild type male mice at age of 5 weeks received four different kinds of diets: a normal diet, high-fat diet (HFD), or HFD supplemented with 1% or 3% (wt:wt) lyophilized MCA for 10 weeks. Body weight, adipose tissue and liver weight, serum biochemical parameters, glucose tolerance and liver lipids were measured. Gut microbial composition was analyzed.Results MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver inflammation were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of AMPK and PPAR-alpha signaling pathway in the human fatty liver HuS-E/2 cell model. Supplementation with MCA resulted in microbiota populations changed significantly.Conclusion Our data indicate that dietary MCA is involved in the prevention of HFD-induced adiposity, insulin resistance and nonalcoholic fatty liver disease and altered the microbial contents of the gut and modulated microbial dysbiosis in the host.

Download Full-text

Effect of Seyoeum on Obesity, Insulin Resistance, and Nonalcoholic Fatty Liver Disease of High-Fat Diet-Fed C57BL/6 Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4658543 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Hyun-Young Na ◽

Mi Hyeon Seol ◽

Mia Kim ◽

Byung-Cheol Lee

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Insulin Receptor ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Obese Mice ◽

High Fat ◽

Nonalcoholic Fatty Liver

Background. This study was performed to evaluate the effect of Seyoeum (SYE), a novel herbal meal replacement, on insulin resistance and nonalcoholic fatty liver disease (NAFLD) in obese mice fed with a high-fat diet (HFD).Methods. SYE contained six kinds of herbal powder such asCoix lacryma-jobi,Oryza sativa,Sesamum indicum,Glycine max,Liriope platyphylla,andDioscorea batatas. Male C57BL/6 mice were divided into four groups: normal chow (NC), HFD, SYE, and HFD plus SYE (HFD + SYE). The mice in groups other than NC were fed HFD for 9 weeks to induce obesity and then were fed each diet for 6 weeks. Clinical markers related to obesity, diabetes, and NAFLD were examined and gene expressions related to inflammation and insulin receptor were determined.Results. Compared with HFD group, body weight, serum glucose, serum insulin, HOMA-IR, total cholesterol, triglyceride, epididymal fat pad weight, liver weight, and inflammatory gene expression were significantly reduced in SYE group. Insulin receptor gene expression increased in SYE group.Conclusions. Based on these results, we conclude that SYE improved obesity and insulin resistance in high-fat fed obese mice. Our findings suggest that SYE could be a beneficial meal replacement through these antiobesity and anti-insulin resistance effects.

Download Full-text

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

Nutrients ◽

10.3390/nu8020083 ◽

2016 ◽

Vol 8 (2) ◽

pp. 83 ◽

Cited By ~ 12

Author(s):

Eunhui Seo ◽

Yoon Sin Oh ◽

Hee-Sook Jun

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Seed Extract ◽

Obese Mice ◽

Psoralea Corylifolia ◽

High Fat ◽

Nonalcoholic Fatty Liver

Download Full-text

Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats

Chinese Journal of Natural Medicines ◽

10.1016/s1875-5364(18)30074-8 ◽

2018 ◽

Vol 16 (6) ◽

pp. 411-417 ◽

Cited By ~ 3

Author(s):

Li-Li MA ◽

Yan-Yan YUAN ◽

Ming ZHAO ◽

Xin-Rong ZHOU ◽

Tashina Jehangir ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

High Fat ◽

Nonalcoholic Fatty Liver

Download Full-text

Salidroside and Curcumin Formula Prevents Liver Injury in Nonalcoholic Fatty Liver Disease in Rats

Annals of Hepatology ◽

10.5604/01.3001.0012.2113 ◽

2018 ◽

Vol 17 (5) ◽

pp. 0-10

Author(s):

Hong-Shan Li ◽

Hao Ying ◽

Zhe-Yun He

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Lipid Deposition ◽

Model Group ◽

High Fat ◽

Nonalcoholic Fatty Liver

Introduction and aim. Salidroside and curcumin (SC) formula could alleviate lipid deposition in high fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the mechanisms are still unknown, and the magnitude of potential therapeutic benefit remains understudied. Material and methods. The rats were treated with high fat diet for 14 weeks to induce NAFLD. The experiment was divided into control, model (NAFLD), SC formula and rosiglitazone groups (n = 7 in each group). Hematoxylin-eosin (H&E) staining was applied to detect liver morphological changes. Biochemical, metabolic indices and inflammation factors in liver tissue and serum were detected. Additionally, the activities of related enzymes were detected by enzyme-linked immunosorbent assay. Results. In the established rat model, typical lipid deposition and liver steatosis were observed. Liver triglyceride, free fatty acids, sera alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fasting insulin, fasting blood glucose and homeostasis model assessment of insulin resistance were elevated in model group. Liver malondialdehyde was significantly elevated, while superoxide dismutase was significantly decreased in model group, compared with control. Moreover, tumor necrosis factor-α and Interleukin-1 were significantly produced in model group, compared with control. As a mechanism, high fat diet decreased tissue AMP-activated protein kinase (AMPK), phosphorylated AMPK, carnitine palmitoyltransferase 1 and increased inacetyl-CoA carboxylase (ACCase), phosphorylated ACCase. Importantly, these abnormal changes caused by high fat diet were reduced by SC formula administration. Conclusion. SC formula could ameliorate the injury caused by high fat diet. The effect was likely mediated via its influence on insulin resistance, lipid peroxidation injury and AMPK signaling pathway.

Download Full-text

Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet

BioMed Research International ◽

10.1155/2020/2947549 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Ningjing Zhang ◽

Junxian Tao ◽

Lijun Gao ◽

Yan Bi ◽

Ping Li ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Structural Changes ◽

High Fat ◽

Nonalcoholic Fatty Liver

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.

Download Full-text

Da-Chai-Hu Decoction Ameliorates High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Through Remodeling the Gut Microbiota and Modulating the Serum Metabolism

Frontiers in Pharmacology ◽

10.3389/fphar.2020.584090 ◽

2020 ◽

Vol 11 ◽

Author(s):

Huantian Cui ◽

Yuting Li ◽

Yuming Wang ◽

Lulu Jin ◽

Lu Yang ◽

...

Keyword(s):

Liver Disease ◽

16S Rrna ◽

Gut Microbiota ◽

Fatty Liver ◽

Metabolic Pathways ◽

High Fat Diet ◽

Fatty Liver Disease ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Rrna Sequencing

The dysbiosis in gut microbiota could affect host metabolism and contribute to the development of nonalcoholic fatty liver disease (NAFLD). Da-Chai-Hu decoction (DCH) has demonstrated protective effects on NAFLD, however, the exact mechanisms remain unclear. In this study, we established a NAFLD rat model using a high fat diet (HFD) and provided treatment with DCH. The changes in gut microbiota post DCH treatment were then investigated using 16S rRNA sequencing. Additionally, serum untargeted metabolomics were performed to examine the metabolic regulations of DCH on NAFLD. Our results showed that DCH treatment improved the dyslipidemia, insulin resistance (IR) and ameliorated pathological changes in NAFLD model rats. 16S rRNA sequencing and untargeted metabolomics showed significant dysfunction in gut microbiota community and serum metabolites in NAFLD model rats. DCH treatment restored the dysbiosis of gut microbiota and improved the dysfunction in serum metabolism. Correlation analysis indicated that the modulatory effects of DCH on the arachidonic acid (AA), glycine/serine/threonine, and glycerophospholipid metabolic pathways were related to alterations in the abundance of Romboutsia, Bacteroides, Lactobacillus, Akkermansia, Lachnoclostridium and Enterobacteriaceae in the gut microflora. In conclusion, our study revealed the ameliorative effects of DCH on NAFLD and indicated that DCH’s function on NAFLD may link to the improvement of the dysbiosis of gut microbiota and the modulation of the AA, glycerophospholipid, and glycine/serine/threonine metabolic pathways.

Download Full-text

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00249.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. G634-G642 ◽

Cited By ~ 85

Author(s):

Zhigang Wang ◽

Tong Yao ◽

Maria Pini ◽

Zhanxiang Zhou ◽

Giamila Fantuzzi ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Control Diet ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Betaine Supplementation

Adipose tissue dysfunction, featured by insulin resistance and/or dysregulated adipokine production, plays a central role not only in disease initiation but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Promising beneficial effects of betaine supplementation on nonalcoholic fatty liver disease (NAFLD) have been reported in both clinical investigations and experimental studies; however, data related to betaine therapy in NAFLD are still limited. In this study, we examined the effects of betaine supplementation on hepatic fat accumulation and injury in mice fed a high-fat diet and evaluated mechanisms underlying its hepatoprotective effects. Male C57BL/6 mice weighing 25 ± 0.5 (SE) g were divided into four groups (8 mice/group) and started on one of four treatments: control diet, control diet supplemented with betaine, high-fat diet, and high-fat diet supplemented with betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Our results showed that long-term high-fat feeding caused NAFLD in mice, which was manifested by excessive neutral fat accumulation in the liver and elevated plasma alanine aminotransferase levels. Betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test, and corrected abnormal adipokine (adiponectin, resistin, and leptin) productions. Specifically, betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signal-regulated kinases 1/2 and protein kinase B activations. In adipocytes freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function.

Download Full-text

Effect of Alkaloids from Nelumbinis Plumula against Insulin Resistance of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Journal of Diabetes Research ◽

10.1155/2016/3965864 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Yong Xie ◽

Yi Zhang ◽

Zebin Guo ◽

Hongliang Zeng ◽

Baodong Zheng

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Inflammatory Cytokines ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Enzyme Linked Immunosorbent Assay ◽

High Fat ◽

Nonalcoholic Fatty Liver

This study aimed to investigate the effects of total alkaloids from Nelumbinis Plumula (NPA) on insulin resistance (IR) of high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD). Rats were fed with HFD for 8 weeks to induce NAFLD. Then, the effect of NPA on ameliorating IR in HFD-induced NAFLD was evaluated. Fasting serum insulin was determined using an enzyme-linked immunosorbent assay (ELISA) kit for insulin following the manufacturer’s protocol. Some inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were determined using ELISA kits to assess the inflammatory burden in rats. The results showed that HFD could induce a significant increase in blood glucose and IR in rats. However, rats treated with NPA (400 or 600 mg/kg) showed improved IR and reduction in serum inflammatory cytokines TNF-αand IL-6. Further investigation indicated that NPA could inhibit IR by restoring the insulin receptor substrate-1 (IRS-1) and suppressing the expression of c-Jun N-terminal kinase (JNK) phosphorylation. The present results supported the view that the pathogenesis of NAFLD was complex with inflammation, together with increasing serum glucose and IR. Also, JNK and IRS phosphorylation were suggested for their involvement in the modulating of IR during NAFLD progression. Therefore, NPA may serve as a potential natural remedy against IR in NAFLD.

Download Full-text