Fish oil supplementation to a high-fat diet improves both intestinal health and the systemic obese phenotype.

Impaired intestinal health characterized by a dysbiotic microbial community and a dysfunctional epithelial barrier contributes to host inflammation and metabolic dysfunction in obesity. Fish oil (FO)-derived n-3 polyunsaturated fatty acids have been shown to improve aspects of the obese phenotype; however, their effect on obese intestinal health is unknown. This study aimed to determine the effect of dietary FO on the intestinal microenvironment, including the microbial community and epithelial barrier, in a mouse model of high-fat diet induced obesity and metabolic dysfunction. Male C57BL/6 mice were fed (12 weeks) either a high-fat diet (HF, 60% fat as kcal) or an isocaloric HF supplemented with Menhaden FO (5.3% kcal, HF + FO). 16S rRNA sequencing was used to determine changes in fecal microbiota. Intestinal (ileum and colon) and epididymal adipose tissue RNA was used to assess biomarkers of barrier integrity and inflammatory status, respectively. Serum was used to assess adipokine concentrations and insulin resistance. HF + FO diet altered the fecal microbiota by decreasing the abundance of Firmicutes and increasing the abundance of members of the Bacteroidetes phyla, as well as increasing the abundance of antiobesogenic Akkermansia muciniphila, compared to HF. Intestinal epithelial barrier functions were improved by HF + FO evidenced by increased mRNA expression of tight junction components, antimicrobial defenses and mucus barrier components. HF + FO-fed mice exhibited improvements in homeostatic model assessment of insulin resistance, oral glucose tolerance and serum adipokine concentrations and epididymal mRNA expression (increased adiponectin and decreased leptin) versus HF. HF + FO improved obese intestinal health and attenuated metabolic dysfunction associated with obesity.

Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice.

OBJECTIVE: The consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique phytochemical profile, strong antioxidant potential and purported anti-inflammatory potential. DESIGN: By using metabolic tests coupled with 16S rRNA gene-based taxonomic profiling and faecal microbial transplantation (FMT), we have assessed the effect of a crude extract of camu camu (CC) on obesity and associated immunometabolic disorders in high fat/high sucrose (HFHS)-fed mice. RESULTS: Treatment of HFHS-fed mice with CC prevented weight gain, lowered fat accumulation and blunted metabolic inflammation and endotoxaemia. CC-treated mice displayed improved glucose tolerance and insulin sensitivity and were also fully protected against hepatic steatosis. These effects were linked to increased energy expenditure and upregulation of uncoupling protein 1 mRNA expression in the brown adipose tissue (BAT) of CC-treated mice, which strongly correlated with the mRNA expression of the membrane bile acid (BA) receptor TGR5. Moreover, CC-treated mice showed altered plasma BA pool size and composition and drastic changes in the GM (eg, bloom of Akkermansia muciniphila and a strong reduction of Lactobacillus). Germ-free (GF) mice reconstituted with the GM of CC-treated mice gained less weight and displayed higher energy expenditure than GF-mice colonised with the FM of HFHS controls. CONCLUSION: Our results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.

Diet-induced obesity and associated disorders are prevented by natural bioactive type 1 fish collagen peptides (Naticol®) treatment.

To fight against metabolic disorders such as insulin resistance, new alimentary behaviors are developed. For instance, hyperproteined, gluten-free, or collagen-enriched diets could be preconized in order to reduce the consequences of obesity. In this aim, this study evaluates the potential effects of warm sea fish collagen peptides (Naticol®) on representative metabolic and inflammatory parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat diet (HFD) were submitted or not to specific collagen peptides in drinking water (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and insulin sensitivity were followed up. Effects of fish collagen peptides on various blood parameters reflecting the metabolism status were also measured (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte inflammation. Results showed that HFD-fed mice supplemented by fish collagen peptides exhibited a significant lower increase in body weight as soon as the twelfth week of treatment whereas no effect of the peptide was observed in CD fed mice. In line with this result, a weaker increase in fat mass in HFD-fed mice supplemented with Naticol® at both 9 and 18 weeks of treatment was also observed. In spite of this resistance to obesity promoted by fish collagen peptides treatment, no difference in glucose tolerance was found between groups whereas mice treated with Naticol® exhibited a lower basal glycemia. Also, even if no effect of the treatment on adipocyte lipolysis was found, a decrease of inflammatory cytokines was retrieved in collagen-supplemented group arguing for a potential better insulin sensitivity. Altogether, these results need to be completed but are the first describing a benefic role of warm sea fish collagen peptides in a context of metabolic disease paving the route for a potential utilization in human obesity-associated disorders.

Omega-3 fatty acids in obesity and metabolic syndrome: a mechanistic update.

Strategies to reduce obesity have become public health priorities as the prevalence of obesity has risen in the United States and around the world. While the anti-inflammatory and hypotriglyceridemic properties of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) are well known, their antiobesity effects and efficacy against metabolic syndrome, especially in humans, are still under debate. In animal models, evidence consistently suggests a role for n-3 PUFAs in reducing fat mass, particularly in the retroperitoneal and epididymal regions. In humans, however, published research suggests that though n-3 PUFAs may not aid weight loss, they may attenuate further weight gain and could be useful in the diet or as a supplement to help maintain weight loss. Proposed mechanisms by which n-3 PUFAs may work to improve body composition and counteract obesity-related metabolic changes include modulating lipid metabolism; regulating adipokines, such as adiponectin and leptin; alleviating adipose tissue inflammation; promoting adipogenesis and altering epigenetic mechanisms.

Astaxanthin inhibits inflammation and fibrosis in the liver and adipose tissue of mouse models of diet-induced obesity and nonalcoholic steatohepatitis.

The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0.015% ASTX (AHF/HS/HC) for 18 weeks. Compared to LF, HF/HS significantly increased plasma total cholesterol, triglyceride and glucose, which were lowered by ASTX. ASTX decreased hepatic mRNA levels of markers of macrophages and fibrosis in both models. The effect of ASTX was more prominent in NASH than DIO mice. In epididymal fat, ASTX also decreased macrophage infiltration and M1 macrophage marker expression, and inhibited hypoxia-inducible factor 1-α and its downstream fibrogenic genes in both mouse models. ASTX significantly decreased tumor necrosis factor α mRNA in the splenocytes from DIO mice upon lipopolysaccharides stimulation compared with those from control mice fed an HF/HS diet. Additionally, ASTX significantly elevated the levels of genes that regulate fatty acid ß-oxidation and mitochondrial biogenesis in the skeletal muscle compared with control obese mice, whereas no differences were noted in adipose lipogenic genes. Our results indicate that ASTX inhibits inflammation and fibrosis in the liver and adipose tissue and enhances the skeletal muscle's capacity for mitochondrial fatty acid oxidation in obese mice.

Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity.

A high-fish-oil diet prevents adiposity and modulates white adipose tissue inflammation pathways in mice.

Fish oil improves obesity and its comorbidities, but its mechanisms of action remain unknown. We evaluate the effects of a diet rich in fish oil in white adipose tissue (WAT) inflammation pathways, renin-angiotensin system (RAS) and mitogen-activated protein kinases (MAPKs). To achieve our aims, four groups of male C57BL/6 mice were fed different diets: standard chow diet (SC; 10% energy from fat), SC+fish oil diet (SC-FO; 10% energy from fat), high-fat lard diet (HF-L; 50% energy from lard) and HF fish oil diet (HF-FO; 50% energy from fish oil). We evaluated body mass, epididymal fat pad mass, food intake and glucose tolerance. In WAT, we assessed adipocyte hypertrophy, monocyte chemotactic protein-1 immunofluorescence, and gene and protein expression of insulin signaling, inflammation, MAPKs, RAS, peroxisome proliferator-activated receptors (PPARs) and AMP-activated protein kinase (AMPK). In relation to the results, the HF-L group, as expected, showed elevated body mass and adiposity, glucose intolerance and hypertrophied adipocytes. In WAT, we found a defect in insulin signaling, infiltration of macrophages and inflammatory markers with the associated activation of MAPKs and local RAS. On the contrary, the HF-FO group did not present increased body mass, adiposity or glucose intolerance. In this group, insulin signaling, macrophage infiltration and inflammation were reduced in WAT in comparison with the HF-L group. We also observed decreases of MAPKs and local RAS and elevation of PPAR and AMPK. In summary, fish oil activates PPAR (the three isoforms) and AMPK, decreases WAT insulin resistance and inflammation, and inhibits MAPK and RAS pathways activation.

Oral administration of the milk casein-derived tripeptide Val-Pro-Pro attenuates high-fat diet-induced adipose tissue inflammation in mice.

Inflammation of adipose tissue triggers the metabolic syndrome, atherosclerosis and CHD. In the present study, we investigated whether the milk casein-derived tripeptide valine-proline-proline (VPP) has an anti-inflammatory effect on the adipose tissue of high-fat diet (HFD)-fed mice. Male C57BL/6J mice (7 weeks of age) were fed ad libitum with either a HFD and plain tap water (HFD group) or a HFD and water containing 0·3 mg VPP/ml (HFD+VPP group) for 10 weeks. The results showed that the expression level of CD18 in the peripheral blood monocytes of the HFD+VPP group was significantly decreased compared with the level observed in those of the HFD group. Activated monocytes and pro-inflammatory macrophages were accumulated in the stromal vascular fractions of the adipose tissue from HFD-fed mice, which were significantly decreased in those supplemented with VPP. The formation of crown-like structures rich in pro-inflammatory macrophages was also significantly reduced in the adipose tissue of mice administered with VPP. Real-time PCR analysis revealed that the expression of monocyte chemoattractant protein-1 and that of the pro-inflammatory cytokine IL-6 in adipose tissue tend to be lower in the HFD+VPP group than in the HFD group. These observations indicate that oral administration of VPP exerts an anti-inflammatory effect on the adipose tissue of HFD-fed mice, which may eventually lead to the primary prevention of chronic inflammation-related diseases.