Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice

Abstract

Adipose tissue (AT) has a modulating role in obesity-induced metabolic complications like type 2 diabetes mellitus (T2DM) via the production of so-called adipokines such as leptin, adiponectin, and resistin. The adipokines are believed to influence other tissues and to affect insulin resistance, liver function, and to increase the risk of T2DM. In this study, we examined the impact of intervention with the short-chain fatty acid butyrate following a high-fat diet (HFD) on AT function and other metabolic risk factors associated with obesity and T2DM in mice during mid- and late life. In both mid- and late adulthood, butyrate reduced HFD-induced adipocyte hypertrophy and elevations in leptin levels, which were associated with body weight, and cholesterol and triglyceride levels. HFD feeding stimulated macrophage accumulation primarily in epididymal AT in both mid- and late life adult mice, which correlated with liver inflammation in late adulthood. In late-adult mice, butyrate diminished increased insulin levels, which were related to adipocyte size and macrophage content in epididymal AT. These results suggest that dietary butyrate supplementation is able to counteract HFD-induced detrimental changes in AT function and metabolic outcomes in late life. These changes underlie the obesity-induced elevated risk of T2DM, and therefore it is suggested that butyrate has potential to attenuate risk factors associated with obesity and T2DM.

High Fat-High Fructose Diet-Induced Changes in the Gut Microbiota Associated with Dyslipidemia in Syrian Hamsters

“…Low-fat/high-fructose diet fed hamsters also exhibited an increase in levels of the butyrate-producing bacterium, Butryimonas [ 75 ]. Butyrate levels are linked to improved metabolite outcomes both in humans and in animal studies, by acting as a regulator of adipocytes [ 76 , 77 ]. Butyrate supplementation has also been found to improve the dyslipidemia caused by a high-fat diet in mice [ 78 ].…”

The Protective Role of Butyrate against Obesity and Obesity-Related Diseases

“…Butyrate could act as a regulator of body weight: a reasonable speculation is that it acts on components of the energy balance, promoting energy expenditure and/or reducing energy intake. Butyrate supplementation was found to have multiple metabolic benefits, including prevention of high-fat diet (HFD)-induced obesity and obesity-associated disorders in the animal model [ 119 , 120 , 121 , 122 , 123 , 124 ]. In addition to its preventive actions in diet-induced disease models, butyrate is also effective in treating obesity through the promotion of energy expenditure and the induction of mitochondrial function: the mechanism of butyrate action for obesity is related to the activation of AMPK, increasing ATP consumption, and the induction of PGC-1α activity, the molecular mechanism by which butyrate stimulates mitochondrial function in association with up-regulated expression of genes involved in lipolysis and fatty acid β-oxidation [ 125 , 126 , 127 ].…”

Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease

“…In rats on a high-fat diet, butyrate supplementation induced the activation of AMP-activated 5 Protein Kinase (AMPK) and glucose transporter 4 (GLUT4) in the adipose tissue, attenuated diet-induced dysbiosis, promoted biosynthesis of resolvin E1 and lipoxin (anti-inflammatory lipid mediators) [175], attenuated weight gain, adiposity, adipocyte hypertrophy, inflammation, and leptin secretion [176]. In the same animal model, butyrate supplementation appears to induce lipolysis in WAT mediated by activation of β3-adrenergic receptors [177] and regulates gene expression related to intestinal cholesterol absorption resulting in attenuation of atherosclerosis [178].…”