Metformin and berberine prevent olanzapine-induced weight gain in rats. Hu Yueshan,Young Alan J,Ehli Erik A,Nowotny Dustin,Davies Paige S,Droke Elizabeth A,Soundy Timothy J,Davies Gareth E PloS one Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure. 10.1371/journal.pone.0093310
    Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight. Horvath Carla,Wolfrum Christian The Proceedings of the Nutrition Society Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements. 10.1017/S0029665120006928
    Phytochemicals as potential candidates to combat obesity via adipose non-shivering thermogenesis. Li Hanbing,Qi Jiameng,Li Linghuan Pharmacological research Obesity is a chronic metabolic disease caused by a long-term imbalance between energy intake and expenditure. The discovery of three different shades of adipose tissues has implications in terms of understanding the pathogenesis and potential interventions for obesity and its related complications. Fat browning, as well as activation of brown adipocytes and new beige adipocytes differentiated from adipogenic progenitor cells, are emerging as interesting and promising methods to curb obesity because of their unique capacity to upregulate non-shivering thermogenesis. This capacity is due to catabolism of stored energy to generate heat through the best characterized thermogenic effector uncoupling protein 1 (UCP1). A variety of phytochemicals have been shown in the literature to contribute to thermogenesis by acting as chemical uncouplers, UCP1 inducers or regulators of fat differentiation and browning. In this review, we summarize the mechanisms and strategies for targeting adipose-mediated thermogenesis and highlight the role of phytochemicals in targeting adipose thermogenesis to fight against obesity. We also discuss proposed targets for how these phytochemical molecules promote BAT activity, WAT browning and beige cell development, thereby offering novel insights into interventional strategies of how phytochemicals may help prevent and manage obesity via adipose thermogenesis. 10.1016/j.phrs.2019.104393
    Berberine activates thermogenesis in white and brown adipose tissue. Zhang Zhiguo,Zhang Huizhi,Li Bo,Meng Xiangjian,Wang Jiqiu,Zhang Yifei,Yao Shuangshuang,Ma Qinyun,Jin Lina,Yang Jian,Wang Weiqing,Ning Guang Nature communications Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity. 10.1038/ncomms6493
    Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis. Okla Meshail,Kim Jiyoung,Koehler Karsten,Chung Soonkyu Advances in nutrition (Bethesda, Md.) Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes. Despite advances in knowledge regarding the developmental lineage and transcriptional regulators of brown and beige adipocytes, our current understanding of environmental modifiers of BAT thermogenesis, such as diet, is limited. In this review, we consolidated the latest research on dietary molecules that may serve to promote BAT thermogenesis. Here, we summarized the thermogenic function of selected phytochemicals (e.g., capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids (e.g., fish oil and conjugated linoleic acids), and all- retinoic acid, a vitamin A metabolite. We also delineated the proposed mechanisms whereby these dietary molecules promote BAT activity and/or browning of white adipose tissue. Characterizing thermogenic dietary factors may offer novel insight into revising nutritional intervention strategies aimed at obesity and diabetes prevention and management. 10.3945/an.116.014332
    Dietary polyphenols and their roles in fat browning. Silvester Allwin Jennifa,Aseer Kanikkai Raja,Yun Jong Won The Journal of nutritional biochemistry Discovery of the presence of brown adipose tissue (BAT) in newborn babies and adult humans, especially constitutively active brown fat or inducible beige fat, has led to the investigation of strategies employing BAT aimed at the development of novel therapeutic avenues for combating obesity and diabetes. Such antiobesity therapeutic tools include pharmaceutical and nutraceutical dietary polyphenols. Although there have been emerging notable advances in knowledge of and an increased amount of research related to brown and beige adipocyte developmental lineages and transcriptional regulators, current knowledge regarding whether and how food factors and environmental modifiers of BAT influence thermogenesis has not been extensively investigated. Therefore, in this review, we summarized recent updates on the exploration of dietary polyphenols while paying attention to the activation of BAT and thermogenesis. Specifically, we summarized findings pertaining to BAT metabolism, white adipose tissue (WAT) browning and thermogenic function of polyphenols (e.g., flavan-3-ols, green tea catechins, resveratrol, capsaicin/capsinoids, curcumin, thymol, chrysin, quercetin and berberine) that may foster a relatively safe and effective therapeutic option to improve metabolic health. We also deciphered the underlying proposed mechanisms through which these dietary polyphenols facilitate BAT activity and WAT browning. Characterization of thermogenic dietary factors may offer novel insight enabling revision of nutritional intervention strategies aimed at obesity and diabetes prevention and management. Moreover, identification of polyphenolic dietary factors among plant-derived natural compounds may provide information that facilitates nutritional intervention strategies against obesity, diabetes and metabolic syndrome. 10.1016/j.jnutbio.2018.09.028