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This study was conducted to evaluate the anti-obesity effects of long-term taurine supplementation in a mild obese ICR mouse model and to study the mechanism by which taurine induces weight loss. Three groups of male ICR mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with 2% taurine in drinking water for 28 weeks. Body weight was measured every week. Metabolic, behavioral, and physiological monitoring were carried out using PhenoMaster at 28 weeks. Interscapular brown fat (BAT), inguinal white fat tissue (WAT), and quadriceps muscle were analyzed and compared to assess the change of gene expression related to adipogenesis. Taurine supplementation showed the trend of anti-obesity effect in ICR mice fed an HFD for 28 weeks. HFD-fed mice did not show significant difference of oxygen consumption (VO2), energy expenditure (EE), respiratory exchange rate (RER), and locomotive activity compared with those of normal chow diet fed mice. The expression of adipogenesis-related genes such as PPAR-α, PPAR-γ, C/EBP-α, C/EBP-β, and AP2 increased in BAT and WAT, but not in muscle tissue. Taurine supplementation showed the downregulation of these genes in WAT but not in BAT or muscle. Consistently, the expression of taurine transporter (TauT) and adipocyte-specific genes such as adiponectin, leptin, and IL-6 was regulated in a similar pattern by taurine supplementation. Long-term taurine supplementation causes weight loss, most likely by inhibiting adipogenesis in WAT. TauT expression may be involved in the expression of various genes regulated by taurine supplementation. [ABSTRACT FROM AUTHOR]

AMP-activated protein kinase (AMPK) plays a key role in controlling energy metabolism in response to physiological and nutritional status. Although AMPK activation has been proposed as a promising molecular target for treating obesity and its related comorbidities, the use of pharmacological AMPK activators has been met with contradictory therapeutic challenges. Here we show a regulatory mechanism for AMPK through its ubiquitination and degradation by the E3 ubiquitin ligase makorin ring finger protein 1 (MKRN1). MKRN1 depletion promotes glucose consumption and suppresses lipid accumulation due to AMPK stabilisation and activation. Accordingly, MKRN1-null mice show chronic AMPK activation in both liver and adipose tissue, resulting in significant suppression of diet-induced metabolic syndrome. We demonstrate also its therapeutic effect by administering shRNA targeting MKRN1 into obese mice that reverses non-alcoholic fatty liver disease. We suggest that ubiquitin-dependent AMPK degradation represents a target therapeutic strategy for metabolic disorders. AMPK activation has been suggested as treatment for obesity and its complications. Here the authors show that the ubiquitin ligase MKRN1 binds to AMPK and mediates its ubiquitination and degradation. Loss of MKRN1 leads to AMPK activation, increased glucose consumption and decreased lipid accumulation. [ABSTRACT FROM AUTHOR]