Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota

Abstract Obesity is a major risk factor for type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease that arises from a caloric surplus of as little as 10–30 kcal per day. And while increased consumption of energy dense foods and reduced physical activity are commonly thought to be the major contributors to this caloric imbalance, diet-induced thermogenesis is a quantitatively important component of the energy balance equation. In adult humans, recent studies have indicated that diet-induced thermogenesis requires the activation of brown adipose tissue (BAT), however, the determinants regulating this process and why they may differ between individuals are not fully understood. We hypothesized that environmental toxicants commonly used as food additives or pesticides might reduce diet-induced thermogenesis through suppression of uncoupling protein 1, the defining protein of human BAT thermogenesis. Through a screening approach of pesticides/toxicants chosen from the Toxcast chem Library, we discovered that the organophosphate insecticide chlorpyrifos potently suppressed the expression of uncoupling protein 1 (UCP1) and mitochondrial respiration in brown adipocytes at concentrations as low as 1 pM. Chloropyrifos-induced suppression of brown adipocyte thermogenesis was also observed in mice fed a diet high in fat and housed at thermoneutrality where it promoted greater obesity, non-alcoholic fatty liver disease and insulin resistance. Reductions in thermogenesis by chlorpyrifos were associated with impaired activation of the β3-adrenergic receptor and protein kinases critical for regulating UCP1 and mitophagy. These data indicate that the commonly used pesticide chlorpyrifos, at doses found within the food supply, suppresses the activation of brown adipose tissue, suggesting that its use may contribute to the obesity epidemic.

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Probiotics and Prebiotics as a Strategy for Non-Alcoholic Fatty Liver Disease, a Narrative Review

Foods ◽

10.3390/foods10081719 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1719

Author(s):

Valentina Castillo ◽

Fernanda Figueroa ◽

Karoll González-Pizarro ◽

Paz Jopia ◽

Claudia Ibacache-Quiroga

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Communicable Disease ◽

Anthropometric Parameters ◽

Alcoholic Fatty Liver ◽

Risks Factors ◽

Alcoholic Fatty Liver Disease ◽

Non Communicable Disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic non-communicable disease, with a prevalence of 25% worldwide. This pathology is a multifactorial illness, and is associated with different risks factors, including hypertension, hyperglycemia, dyslipidemia, and obesity. Beside these predisposing features, NAFLD has been related to changes in the microbiota, which favor the disease progression. In this context, the modulation of the gut microbiota has emerged as a new therapeutic target for the prophylaxis and treatment of NAFLD. This review describes the changes in the gut microbiota associated with NAFLD and the effect of probiotics, prebiotics, and synbiotics on the gut microbiota, liver damage, anthropometric parameters, blood lipids, inflammation markers and insulin resistance in these patients.

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High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs

Scientific Reports ◽

10.1038/s41598-021-82208-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nikolaj H. Schmidt ◽

Pia Svendsen ◽

Julián Albarrán-Juárez ◽

Søren K. Moestrup ◽

Jacob Fog Bentzon

Keyword(s):

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Histopathological Examination ◽

De Novo Lipogenesis ◽

Large Animal ◽

Alcoholic Fatty Liver ◽

High Fructose ◽

Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that has been linked to high-fructose corn syrup consumption with induction of hepatic de novo lipogenesis (DNL) as the suggested central mechanism. Feeding diets very high in fructose (> 60%) rapidly induce several features of NAFLD in rodents, but similar diets have not yet been applied in larger animals, such as pigs. With the aim to develop a large animal NAFLD model, we analysed the effects of feeding a high-fructose (HF, 60% w/w) diet for four weeks to castrated male Danish Landrace-York-Duroc pigs. HF feeding upregulated expression of hepatic DNL proteins, but levels were low compared with adipose tissue. No steatosis or hepatocellular ballooning was seen on histopathological examination, and plasma levels of transaminases were similar between groups. Inflammatory infiltrates and the amount of connective tissue was slightly elevated in liver sections from fructose-fed pigs, which was corroborated by up-regulation of macrophage marker expression in liver homogenates. Supported by RNA-profiling, quantitative protein analysis, histopathological examination, and biochemistry, our data suggest that pigs, contrary to rodents and humans, are protected against fructose-induced steatosis by relying on adipose tissue rather than liver for DNL.

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