Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids

Obesity and its complications—including type 2 diabetes, cardiovascular disease, and certain cancers—constitute a rising global epidemic that has imposed a substantial burden on health and healthcare systems over the years. It is becoming increasingly clear that there is a link between obesity and the gut microbiota. Gut dysbiosis, characterized as microbial imbalance, has been consistently associated with obesity in both humans and animal models, and can be reversed with weight loss. Emerging evidence has shown that microbial-derived metabolites such as short-chain fatty acids (SCFAs)—including acetate, propionate, and butyrate—provide benefits to the host by impacting organs beyond the gut, including adipose tissue. In this review, we summarize what is currently known regarding the specific mechanisms that link gut-microbial-derived SCFAs with adipose tissue metabolism, such as adipogenesis, lipolysis, and inflammation. In addition, we explore indirect mechanisms by which SCFAs can modulate adipose tissue metabolism, such as via perturbation of gut hormones, as well as signaling to the brain and the liver. Understanding how the modulation of gut microbial metabolites such as SCFAs can impact adipose tissue function could lead to novel therapeutic strategies for the prevention and treatment of obesity.

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Short-Chain Fatty Acids Enhance Adipocyte Differentiation in the Stromal Vascular Fraction of Porcine Adipose Tissue

Journal of Nutrition ◽

10.3945/jn.114.198531 ◽

2014 ◽

Vol 144 (12) ◽

pp. 1887-1895 ◽

Cited By ~ 50

Author(s):

Genlai Li ◽

Wen Yao ◽

Honglin Jiang

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Adipocyte Differentiation ◽

Stromal Vascular Fraction ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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Short-chain fatty acids as novel therapeutics for gestational diabetes

Journal of Molecular Endocrinology ◽

10.1530/jme-20-0094 ◽

2020 ◽

Vol 65 (2) ◽

pp. 21-34

Author(s):

Rebecca Roy ◽

Caitlyn Nguyen-Ngo ◽

Martha Lappas

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Insulin Signalling ◽

Short Chain Fatty Acids ◽

Serine Phosphorylation ◽

Short Chain ◽

Low Grade ◽

Chain Fatty Acids

Gestational diabetes mellitus (GDM) affects up to 16% of pregnant women and is associated with significant long-term health detriments for the mother and her offspring. Two central features of GDM are low-grade inflammation and maternal peripheral insulin resistance, therefore therapeutics which target these may be most effective at preventing the development of GDM. Short-chain fatty acids (SCFAs), such as butyrate and propionate, are metabolites produced from the fermentation of dietary fibre by intestinal microbiota. SCFAs possess anti-inflammatory, anti-obesity and anti-diabetic properties. Therefore, this study aimed to investigate the effect of SCFAs on inflammation and insulin signalling defects in an in vitro model of GDM. Human placenta, visceral adipose tissue (VAT) and s.c. adipose tissue (SAT) were stimulated with either the pro-inflammatory cytokine TNF or bacterial product lipopolysaccharide (LPS). The SCFAs butyrate and propionate blocked TNF- and LPS-induced mRNA expression and secretion of pro-inflammatory cytokines and chemokines in placenta, VAT and SAT. Primary human cells isolated from skeletal muscle were stimulated with TNF to assess the effect of SCFAs on inflammation-induced defects in the insulin signalling pathway. Butyrate and propionate were found to reverse TNF-induced increases in IRS-1 serine phosphorylation and decreases in glucose uptake. Butyrate and propionate exerted these effects by preventing ERK activation. Taken together, these results suggest that the SCFAs may be able to improve insulin sensitivity and prevent inflammation induced by sterile or bacterial inflammation. Future in vivo studies are warranted to investigate the efficacy and safety of SCFAs in preventing insulin resistance and inflammation associated with GDM.

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Effects of Different Concentrations of Ganpu Tea on Fecal Microbiota and Short Chain Fatty Acids in Mice

Nutrients ◽

10.3390/nu13113715 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3715

Author(s):

Chen Wang ◽

Zhipeng Gao ◽

Yujiao Qian ◽

Xiang Li ◽

Jieyi Wang ◽

...

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dietary Therapy ◽

Health Food ◽

Intestinal Microorganisms ◽

Positive Effects ◽

Chain Fatty Acids

Ganpu tea is composed of tangerine peel and Pu-erh tea. Current research suggests that both products can interact with gut microbes and thus affect health. However, as a kind of compound health food, little information is available about the effect of Ganpu tea on intestinal microorganisms. In this study, the basic physiological parameters (body weight, white adipose tissue and serum fat), the regulation of intestinal microorganisms and content of short-chain fatty acids (SCFAs) in feces of healthy mice were studied. The Ganpu tea can reduce the weight gain of mice and the increase in white adipose tissue (p < 0.01). After the intake of Ganpu tea, the abundance of Bacteroidetes increased (p < 0.05), whereas that of Firmicutes decreased (p < 0.01), indicating the latent capacity of Ganpu tea in adjusting the gut microbiota. Moreover, Ganpu tea differentially affected the content of different types of SCFAs in feces. Ganpu tea at the lowest concentrations showed positive effects on the concentrations of SCFAs such as acetic acid and propionic acid, whereas the concentration of butyric acid was decreased. For branched short-chain fatty acids (BSCFAs) such as isobutyric acid, isovaleric acid, etc., Ganpu tea reduced their concentrations. Our results indicated that Ganpu tea may have positive effects on preventing obesity in humans, but further research is needed before introducing such dietary therapy.

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The interaction of short-chain fatty acids with adipose tissue: relevance for prevention of type 2 diabetes

Beneficial Microbes ◽

10.3920/bm2010.0028 ◽

2010 ◽

Vol 1 (4) ◽

pp. 433-437 ◽

Cited By ~ 47

Author(s):

H. Roelofsen ◽

M. Priebe ◽

R. Vonk

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Adipose Tissue ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Physiological Relevance ◽

Anti Inflammatory ◽

Chain Fatty Acids

Short chain fatty acids (SCFA) are the main bacterial metabolites of colonic fermentation processes. The physiological relevance of the SCFA for the host outside the gastrointestinal tract is getting increased attention. In this review we will focus on the effect of SCFA on inflammation processes in the host in relation to insulin resistance. Obesity has been associated with a pro-inflammatory state of the adipose tissue that is associated with whole body insulin resistance leading to type 2 diabetes. Recently, two G protein-coupled receptors (GPCR) for SCFA, GPCR 41 and GPCR43, were described that are mainly expressed by immune cells but also by adipose tissue. Propionate can induce the satiety hormone leptin and reduce expression of inflammatory cytokines and chemokines indicating that SCFA have anti-inflammatory effects in human adipose tissue. In addition, in human nutritional experiments we observed that whole grain products could counteract a glucose-induced tumour necrosis factor α and interleukin-6 increase which was associated with increased plasma butyrate concentrations. This suggests that dietary fibre can produce a SCFA profile that could have anti-inflammatory effects in the body. The physiological relevance of these observations especially in relation to obesity-associated inflammation and insulin resistance is discussed.

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The Interaction of Short-Chain Fatty Acids (SCFA) With Adipose Tissue; Relevance for Systemic Inflammation

Gastroenterology ◽

10.1016/s0016-5085(11)63571-3 ◽

2011 ◽

Vol 140 (5) ◽

pp. S-860 ◽

Cited By ~ 4

Author(s):

Roel J. Vonk ◽

Marion Priebe ◽

Kees Meijer ◽

Koen Venema ◽

Han Roelofsen

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Systemic Inflammation ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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The fermentable fibre inulin increases postprandial serum short-chain fatty acids and reduces free-fatty acids and ghrelin in healthy subjects

Applied Physiology Nutrition and Metabolism ◽

10.1139/h09-119 ◽

2010 ◽

Vol 35 (1) ◽

pp. 9-16 ◽

Cited By ~ 163

Author(s):

Joshua Tarini ◽

Thomas M.S. Wolever

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Free Fatty Acids ◽

Dietary Fibre ◽

Healthy Subjects ◽

Gut Hormones ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

It is thought that diets high in dietary fibre are associated with reduced risk for type 2 diabetes, at least in part because the short-chain fatty acids (SCFAs) produced during the colonic fermentation of fibre beneficially influence circulating concentrations of free-fatty acids (FFAs) and gut hormones involved in the regulation of blood glucose and body mass. However, there is a paucity of data showing this sequence of events in humans. Thus, our objective was to determine the effect of the fermentable fibre inulin on postprandial glucose, insulin, SCFA, FFA, and gut hormone responses in healthy subjects. Overnight fasted healthy subjects (n = 12) were studied for 6 h after consuming 400 mL drinks, containing 80 g high-fructose corn syrup (80HFCS), 56 g HFCS (56HFCS), or 56 g HFCS plus 24 g inulin (Inulin), using a randomized, single-blind, crossover design. A standard lunch was served 4 h after the test drink. Glucose and insulin responses after Inulin did not differ significantly from those after 80HFCS or 56HFCS. Serum acetate, propionate, and butyrate were significantly higher after Inulin than after HFCS drinks from 4–6 h. FFAs fell at a similar rate after all 3 test drinks, but were lower after Inulin than after 56HFCS at 4 h (0.40 ± 0.06 vs. 0.51 ± 0.06 mmol·L–1; p < 0.05). Compared with 56HFCS, Inulin significantly increased plasma glucagon-like peptide-1 concentrations at 30 min, and reduced ghrelin at 4.5 h and 6 h. The results are consistent with the hypothesis that dietary fibre increases the production of colonic SCFAs, which may reduce type 2 diabetes risk by reducing postprandial FFAs and favorably affecting gut hormones, which regulate food intake.

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Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids

Nutrients ◽

10.3390/nu13020481 ◽

2021 ◽

Vol 13 (2) ◽

pp. 481

Author(s):

Habeeb Alhabeeb ◽

Ali AlFaiz ◽

Emad Kutbi ◽

Dayel AlShahrani ◽

Abdullah Alsuhail ◽

...

Keyword(s):

Fatty Acids ◽

Gut Hormones ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Novel Treatments ◽

Potential Possibility ◽

Treatment Of Obesity ◽

Underlying Mechanisms ◽

Chain Fatty Acids

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.

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