Berberine Ameliorates Obesity by Inducing GDF15 Secretion by Brown Adipocytes

Abstract

Berberine (BBR), which is a compound derived from the Chinese medicinal plant Coptis chinensis, promotes weight loss, but the molecular mechanisms are not well understood. Here, we show that BBR increases the serum level of growth differentiation factor 15 (GDF15), which is a stress response cytokine that can reduce food intake and lower body weight in diet-induced obese (DIO) mice. The body weight and food intake of DIO mice were decreased after BBR treatment, and the weight change was negatively correlated with the serum GDF15 level. Further studies show that BBR induced GDF15 mRNA expression and secretion in the brown adipose tissue (BAT) of DIO mice and primary mouse brown adipocytes. In addition, we found that BBR upregulates GDF15 mRNA expression and secretion by activating the integrated stress response (ISR) in primary mouse brown adipocytes. Overall, our findings show that BBR lowers body weight by inducing GDF15 secretion via the activation of the ISR in BAT.

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

“…13 Berberine (BBR) is a traditional Chinese herbal medicine that consistently plays an important role in the treatment of metabolic disorders. [14][15][16][17] It has been found in recent years to have clear and long-lasting effects in lowering blood lipid levels, to have advantages over common hypoglycaemic drugs such as sulfonylurea and biguanide, and to have obvious efficacy in reducing the complications associated with various chronic diseases without serious adverse effects such as liver and kidney decompensation, blood abnormalities or hypoglycaemia; thus, it has attracted a great deal of attention from experts and scholars in China and shows great potential for secondary development. [18][19][20] BBR alleviates myocardial ischemia-reperfusion injury, and it has been shown to exert its effects on neuronal injury, cancer, and other diseases through the regulation of miRNAs.…”

Pharmacokinetics, Tissue Distribution and Excretion of Demethyleneberberine, a Metabolite of Berberine, in Rats and Mice

“…Interestingly, the gut microbiota plays a crucial role in mediating the cardiovascular protection provided by berberine [17][18][19]. Importantly, berberine has demonstrated promising potential effects in various areas, such as anti-cancer [20][21][22], anti-diabetic [23][24][25], anti-rheumatoid [26], anti-obesity [27,28] and probone regeneration [29,30]. It also exhibits certain protective effects on the liver [31,32], lung function [33,34] and nerves [35,36].…”