Berberine activates thermogenesis in white and brown adipose tissue

Zhang, Zhiguo; Zhang, Huizhi; Li, Bo; Meng, Xiang-jian; Wang, Jiqiu; Zhang, Yifei; Yao, Shuangshuang; Ma, Qinyun; Jin, Lina; Yang, Jian; Wang, Weiqing; Ning, Guang

doi:10.1038/ncomms6493

Cited by 378 publications

(292 citation statements)

References 69 publications

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“…Above studies indicate that a balance between WAT and BAT is necessary to maintain energy homeostasis and healthy body composition. Recent evidences have associated BAT with non-shivering thermogenesis, lipolysis, fatty acid oxidation, insulin sensitivity, and improved serum lipid profile (Zhang et al 2014). Study conducted by Gray et al showed that hyperinsulinemia precedes insulin resistance in mice lacking pancreatic leptin signaling (Gray et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

Rajan

Shankar

Beg

et al. 2016

Journal of Endocrinology

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The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8 weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes.

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Section: Introductionmentioning

confidence: 99%

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

Rajan

Shankar

Beg

et al. 2016

Journal of Endocrinology

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“…Conversely, prolonged inhibition of adrenergic receptors decreases AMPK activity (25). Accordingly, the plant-derived alkaloid berberine or microRNA-455 enhances brown adipogenesis via activation of AMPK (26,27). In addition, AMPK stimulates glycolysis (28) and coupled respiration-mediated ATP generation in metabolic tissues (29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

Zhu

Ghoshal

Rodrigues

et al. 2016

Journal of Clinical Investigation

156

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“…Thus pharmacological intervention that can reduce insulin hypersecretion and simultaneously alleviate insulin resistance is an attractive strategy to prevent beta-cell dysfunction due to their exhaustion. Berberine exerts hypoglycemic and hypolipidemic action via stimulating glucose uptake, reducing lipogenesis, and increasing energy expenditure in peripheral tissues [8,9,20]. Berberine can also decrease insulin levels in high-fat-fed rats [10].…”

Section: Discussionmentioning

confidence: 99%

Berberine inhibits glucose oxidation and insulin secretion in rat islets

et al. 2018

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Abstract. Glucose promotes insulin secretion primarily via its metabolism and the production of metabolic coupling factors in beta-cells. The activation of AMP-activated protein kinase (AMPK), an energy sensor, results in a decrease in insulin secretion from beta-cells, but its mechanism remains largely unknown. Berberine, an oral anti-diabetic drug, has been shown to activate AMPK in multiple peripheral tissues. Here, we examined the effects of berberine and AMPK activation on insulin secretion and glucose oxidation in rat islets. Our results showed that berberine inhibited glucose-stimulated insulin secretion from rat islets with AMPK activation. When glucose concentration was elevated to 25 mmol/L, the inhibitory action of berberine on insulin secretion disappeared. Furthermore, berberine significantly decreased oxygen consumption rate (OCR) and ATP production induced by high glucose in rat islets. Although adenovirus-mediated overexpression of constituentactivated AMPK markedly decreased GSIS and OCR in rat islets, the inhibition of AMPK by compound C did not reverse berberine-suppressed OCR. In addition, berberine attenuated glucose-stimulated expression of fatty acid synthase. These results indicate that berberine-mediated deceleration of glucose oxidation is tightly link to the decreased insulin secretion in islets independent of AMPK activation and inhibition of fatty acid synthesis may also contribute to the effect of berberine on insulin secretion.

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Berberine activates thermogenesis in white and brown adipose tissue

Cited by 378 publications

References 69 publications

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

Berberine inhibits glucose oxidation and insulin secretion in rat islets

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