Explore the vast range of titles available.

•Probiotics supplementation slowed weight gain in both the high-fat diet (HFD) and high-sucrose diet (HCD) groups.•An HFD is more likely to reduce gut microbiota diversity, whereas an HCD is more likely to alter the bacterial composition related to obesity.•Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced obesity. Gut microbiota plays a crucial role in host energy homeostasis, which is affected by both high-fat diets (HFDs) and high-sucrose diets (HCDs). Probiotics treatment can effectively modulate intestinal microbiota. However, it remains unclear whether probiotics can effectively improve HFD- and HCD-induced microbiota dysbiosis. Mice were fed either an HFD, HCD, or normal diet for 13 wk and administered probiotics during the last 4 wk of the diet. Fecal and cecal samples were collected and analyzed by high-throughput 16S ribosomal RNA sequencing. Body weight increased more in the HFD group compared with the HCD group. Probiotics supplementation slowed weight gain in both the HFD and HCD groups. Both the HFD and HCD reduced microbial diversity, abundance of butyric acid–producing bacteria, and some other beneficial bacteria, including Lactobacillus, Clostridium sensu stricto, Prevotella, and Alloprevotella, but increased conditional pathogenic bacteria, such as Bacteroides, Alistipes, and Anaerotruncus. Probiotics markedly restored the proportions of bacteria affected in the HFD and HCD groups and increased the abundance of microbiota negatively associated with obesity, including Bifidobacterium, Lactococcus, and Akkermansia. In addition, Oscillibacter, Escherichia/Shigella, Acinetobacter, and Blautia significantly increased in the HCD group; Allobaculum, Olsenella, and Ruminococcus were significantly changed in the HFD group. HCD-induced microbiota dysbiosis was more susceptible to probiotics treatment compared with the HFD. Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced obesity.

The consumption of a high-fat, low-carbohydrate diet (ketogenic diet) has diverse effects on health and is expected to have therapeutic value in neurological disorders, metabolic syndrome, and cancer. Recent studies have shown that a ketogenic diet not only pronouncedly shifts the cellular metabolism to pseudo-starvation, but also exerts a variety of physiological functions on various organs through metabolites that act as energy substrates, signaling molecules, and epigenetic modifiers. In this review, we highlight the latest findings on the molecular mechanisms of a ketogenic diet and speculate on the significance of these functions in the context of the epigenome and microbiome. Unraveling the molecular basis of the bioactive effects of a ketogenic diet should provide solid evidence for its clinical application in a variety of diseases including cancer.

A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have drawn inconsistent results. In this study, the unexpected results showed that the refined HFD increased gut microbiota diversity and short-chain fatty acids (SCFAs), causing an increase in energy metabolism. Further analysis revealed these changes were caused by the different fiber content in these two diets. Male C57BL/6J mice (4–5 weeks old) were fed either HFD or refined low-fat diet (LFD) for 14 weeks. The metabolic rates, thermogenesis, gut microbiome, and intestinal SCFAs were tested. The HFD triggered obesity and disturbed glucose homeostasis. Mice fed HFD ingested more fiber than mice fed LFD (p < 0.0001), causing higher intestinal SCFA concentrations related to the increased abundances of specific bacteria in the HFD group. Also, the HFD increased metabolic heat and up-regulated thermogenesis genes uncoupling protein 1(Ucp-1), peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) expression in the brown adipose tissue (BAT). It was revealed by 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Desulfovibrionaceae, Rikenellaceae RC9 gut group, and Mucispirillum, meanwhile, reduced the abundance of Lactobacillus, Bifidobacterium, Akkermansia, Faecalibaculum, and Blautia. The predicted metabolic pathways indicated HFD increased the gene expression of non-absorbed carbohydrate metabolism pathways, as well as the risks of colonization of intestinal pathogens and inflammation. In conclusion, the HFD was obesogenic in male C57BL/6J mice, and increased fiber intake from the HFD drove an increase in gut microbiota diversity, SCFAs, and energy expenditure. Meanwhile, the differences in specific nutrient intake can dissociate broad changes in energy expenditure, gut microbiota, and its metabolites from obesity, raising doubts in the previous studies. Therefore, it is necessary to consider whether differences in specific nutrient intake will interfere with the results of the experiments.

The gut microbiome is an important determinant in various diseases. Here we perform a cross-sectional study of Japanese adults and identify the Blautia genus, especially B. wexlerae , as a commensal bacterium that is inversely correlated with obesity and type 2 diabetes mellitus. Oral administration of B. wexlerae to mice induce metabolic changes and anti-inflammatory effects that decrease both high-fat diet–induced obesity and diabetes. The beneficial effects of B. wexlerae are correlated with unique amino-acid metabolism to produce S-adenosylmethionine, acetylcholine, and l -ornithine and carbohydrate metabolism resulting in the accumulation of amylopectin and production of succinate, lactate, and acetate, with simultaneous modification of the gut bacterial composition. These findings reveal unique regulatory pathways of host and microbial metabolism that may provide novel strategies in preventive and therapeutic approaches for metabolic disorders. Here, the authors inversely associate Blautia wexlerae with obesity and type 2 diabetes mellitus in humans and further show that administration of B. wexlerae to mice decrease both high-fat diet–induced obesity and diabetes via modulating gut microbial metabolism.

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy- cis -12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus -colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites. The gut microbiome is an important regulator of metabolic health. Here the authors show that intestinal bacteria metabolize dietary linoleic acid to 10-hydroxy- cis -12-octadecenoic acid (HYA) which confers host resistance to high fat diet-induced obesity in mice.

The majority of the epidemiological evidence over the past few decades has linked high intake of fats, especially saturated fats, to increased risk of diabetes and cardiovascular disease. However, findings of some recent studies (e.g., the PURE study) have contested this association. High saturated fat diets (HFD) have been widely used in rodent research to study the mechanism of insulin resistance and metabolic syndrome. Two separate but somewhat overlapping models—the diacylglycerol (DAG) model and the ceramide model—have emerged to explain the development of insulin resistance. Studies have shown that lipid deposition in tissues such as muscle and liver inhibit insulin signaling via the toxic molecules DAG and ceramide. DAGs activate protein kinase C that inhibit insulin-PI3K-Akt signaling by phosphorylating serine residues on insulin receptor substrate (IRS). Ceramides are sphingolipids with variable acyl group chain length and activate protein phosphatase 2A that dephosphorylates Akt to block insulin signaling. In adipose tissue, obesity leads to infiltration of macrophages that secrete pro-inflammatory cytokines that inhibit insulin signaling by phosphorylating serine residues of IRS proteins. For cardiovascular disease, studies in humans in the 1950s and 1960s linked high saturated fat intake with atherosclerosis and coronary artery disease. More recently, trials involving Mediterranean diet (e.g., PREDIMED study) have indicated that healthy monounsaturated fats are more effective in preventing cardiovascular mortality and coronary artery disease than are low-fat, low-cholesterol diets. Antioxidant and anti-inflammatory effects of Mediterranean diets are potential mediators of these benefits.

In the past, different types of diet with a generally low-carbohydrate content (< 50–< 20 g/day) have been promoted, for weight loss and diabetes, and the effectiveness of a very low dietary carbohydrate content has always been a matter of debate. A significant reduction in the amount of carbohydrates in the diet is usually accompanied by an increase in the amount of fat and to a lesser extent, also protein. Accordingly, using the term “low carb–high fat” (LCHF) diet is most appropriate. Low/very low intakes of carbohydrate food sources may impact on overall diet quality and long-term effects of such drastic diet changes remain at present unknown. This narrative review highlights recent metabolic and clinical outcomes of studies as well as practical feasibility of low LCHF diets. A few relevant observations are as follows: (1) any diet type resulting in reduced energy intake will result in weight loss and related favorable metabolic and functional changes; (2) short-term LCHF studies show both favorable and less desirable effects; (3) sustained adherence to a ketogenic LCHF diet appears to be difficult. A non-ketogenic diet supplying 100–150 g carbohydrate/day, under good control, may be more practical. (4) There is lack of data supporting long-term efficacy, safety and health benefits of LCHF diets. Any recommendation should be judged in this light. (5) Lifestyle intervention in people at high risk of developing type 2 diabetes, while maintaining a relative carbohydrate-rich diet, results in long-term prevention of progression to type 2 diabetes and is generally seen as safe.

Food is a powerful entrainment cue for circadian clocks in peripheral tissues, and changes in the composition of nutrients have been demonstrated to metabolically reprogram peripheral clocks. However, how food challenges may influence circadian metabolism of the master clock in the suprachiasmatic nucleus (SCN) or in other brain areas is poorly understood. Using high-throughput metabolomics, we studied the circadian metabolome profiles of the SCN and medial prefrontal cortex (mPFC) in lean mice compared with mice challenged with a high-fat diet (HFD). Both the mPFC and the SCN displayed a robust cyclic metabolism, with a strikingly high sensitivity to HFD perturbation in an area-specific manner. The phase and amplitude of oscillations were drastically different between the SCN and mPFC, and the metabolic pathways impacted by HFD were remarkably region-dependent. Furthermore, HFD induced a significant increase in the number of cycling metabolites exclusively in the SCN, revealing an unsuspected susceptibility of the master clock to food stress.

Microplastics (MPs) are small particles of plastic ( in diameter). In recent years, oral exposure to MPs in living organisms has been a cause of concern. Leaky gut syndrome (LGS), associated with a high-fat diet (HFD) in mice, can increase the entry of foreign substances into the body through the intestinal mucosa. We aimed to evaluate the pathophysiology of intestinal outcomes associated with consuming a high-fat diet and simultaneous intake of MPs, focusing on endocrine and metabolic systems. C57BL6/J mice were fed a normal diet (ND) or HFD with or without polystyrene MP for 4 wk to investigate differences in glucose tolerance, intestinal permeability, gut microbiota, as well as metabolites in serum, feces, and liver. In comparison with HFD mice, mice fed the HFD with MPs had higher blood glucose, serum lipid concentrations, and nonalcoholic fatty liver disease (NAFLD) activity scores. Permeability and goblet cell count of the small intestine (SI) in HFD-fed mice were higher and lower, respectively, than in ND-fed mice. There was no obvious difference in the number of inflammatory cells in the SI lamina propria between mice fed the ND and mice fed the ND with MP, but there were more inflammatory cells and fewer anti-inflammatory cells in mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. The expression of genes related to inflammation, long-chain fatty acid transporter, and cotransporter was significantly higher in mice fed the HFD with MPs than in mice fed the HFD without MPs. Furthermore, the genus was significantly more abundant in the intestines of mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. gene expression was decreased when palmitic acid and microplastics were added to the murine intestinal epithelial cell line MODE-K cells, and Muc2 gene expression was increased when IL-22 was added. Our findings suggest that in this study, MP induced metabolic disturbances, such as diabetes and NAFLD, only in mice fed a high-fat diet. These findings suggest that LGS might have been triggered by HFD, causing MPs to be deposited in the intestinal mucosa, resulting in inflammation of the intestinal mucosal intrinsic layer and thereby altering nutrient absorption. These results highlight the need for reducing oral exposure to MPs through remedial environmental measures to improve metabolic disturbance under high-fat diet conditions. https://doi.org/10.1289/EHP11072.

Recent research suggested that taking a high‐fat diet (HFD) may lead to a gut microbiota imbalance and colon tissue damage. This would lead to increased intestinal permeability and consequent constant circulation of low‐grade inflammatory cytokines. Spirulina platensis can protect against HFD‐induced metabolic inflammation and can stimulate the growth of beneficial bacteria in in vitro stool cultures. However, it is unknown whether this beneficial effect acts on intestinal tissues. In this study, rats were fed a high‐fat diet fed with 3% S platensis for 14 weeks. We analysed endotoxin, the composition of the microbiota, inflammation and gut permeability. We found that S platensis decreased the bodyweight and visceral fat pads weight of the HFD‐fed rats. In addition, it lowered the levels of lipopolysaccharide and pro‐inflammatory cytokines in serum. Our results showed that S platensis could largely reduce the relative amount of Proteobacteria and the Firmicutes/Bacteroidetes ratio in faecal samples from HFD‐fed rats. S platensis significantly reduced intestinal inflammation, as shown by decreased expression of myeloid differentiation factor 88 (MyD88), toll‐like receptor 4 (TLR4), NF‐κB (p65) and inflammatory cytokines. S platensis also ameliorated the increased permeability and decreased expression of tight junction proteins in the intestinal mucosa, such as ZO‐1, Occludin and Claudin‐1. Therefore, in HFD‐induced gut dysbiosis rats, S platensis benefits health by inhibiting chronic inflammation and gut dysbiosis, and modulating gut permeability.