Green tea extract increases adiponectin and PPAR α levels to improve hepatic steatosis.

We postulated that Green tea (GT) improvements in non-alcoholic fatty liver disease (NAFLD) are dependent on adiponectin action in the liver. Male wild-type and adiponectin knockout (adipoKO) mice were induced to obesity for 8 weeks with a high-fat diet and then treated with GT for the last 12 weeks of the experimental protocol. Glucose and insulin tolerance tests, indirect calorimetry, histologic analysis of liver sections, and quantification of mRNA of hepatic genes related to glucose or fatty acid metabolism were performed. In vitro, we assessed the mechanism by which GT catechins act to improve hepatic steatosis by measuring lipid accumulation, and transcript levels of lipogenic genes in HepG2 cells treated with GT in the presence of a PPAR antagonist. Additionally, we performed a PPAR transactivation assay in 293T cells to test if catechins could activate PPARs. Different from wild-type mice, adipoKO animals treated with GT and fed a HFD gain body weight and fat mass, that were associated with a decrease in energy expenditure, were insulin resistant, and had no improvements in hepatic steatosis. Increased lipid levels were associated with no modulation of PPARα levels in the liver of adipoKO mice treated with GT. In vitro, we demonstrated GT catechins act to reduce hepatic steatosis in a PPARα-dependent manner, and especially epigallocatechin and epicatechin can indirectly activate PPARα, although it seems they are not direct ligands. By providing the mechanisms by which GT catechins act in the liver to improve steatosis, our data contribute to the discovery of novel therapeutic agents in the management of NAFLD.

Polyphenol-rich green tea extract induces thermogenesis in mice by a mechanism dependent on adiponectin signaling.

Adiponectin is downregulated in obesity negatively impacting the thermogenesis and impairing white fat browning. Despite the notable effects of green tea (GT) extract in the enhancement of thermogenesis, if its effects are being mediated by adiponectin has been scarcely explored. For this purpose, we investigated the role of adiponectin in the thermogenic actions of GT extract by using an adiponectin-knockout mice model. Male wild-type (WT) and knockout (AdipoKO) C57Bl/6 mice (3 months) were divided into 6 groups: mice fed a standard diet+gavage with water (SD WT, and SD AdipoKO), high-fat diet (HFD)+gavage with water (HFD WT, and HFD AdipoKO), and HFD + gavage with 500 mg/kg of body weight (BW) of GT extract (HFD + GT WT, and HFD + GT AdipoKO). After 20 weeks of experimentation, mice were euthanized and adipose tissue was properly removed. Our findings indicate that treatment with GT extract reversed complications of obesity in WT mice by decreasing final BW gain, adiposity index, adipocyte size and insulin resistance (IR). However, the action of the GT extract was not effective in reversing those markers in the AdipoKO mice, although GT acts independently in the reversal of IR. GT-treatment induced enhancement in energy expenditure (EE), BAT thermogenesis, and promoted browning phenotype in the subcutaneous WAT (scWAT) of WT mice. On the other hand, the thermogenic program was markedly impaired in BAT and scWAT of AdipoKO mice. Our outcomes unveiled adiponectin as a key direct signal for GT extract inducing adaptive thermogenesis and browning in scWAT.

Polyphenol-rich green tea extract improves adipose tissue metabolism by down-regulating miR-335 expression and mitigating insulin resistance and inflammation.

Obesity leads to changes in miRNA expression in adipose tissue, and this modulation is linked to the pathophysiology of the disease. Green tea (GT) is a natural source of polyphenols that have been shown to confer health benefits, particularly preventing metabolic diseases. Here, we investigated if the beneficial effects of GT in obesity results from changes in the miRNA profile in white adipose tissue. GT treatment [500 mg/body weight (BW)/12 weeks] increased energy expenditure of high-fat diet-fed mice (16 weeks), leading to reduced weight gain, decreased adiposity, reduced inflammation and improved insulin sensitivity. These phenotypes were associated with a decrease in the expression of miR-335 in the adipose tissue. miR-335 was up-regulated by TNF-α in adipocytes and, in turn, down-regulated genes involved in insulin signaling and lipid metabolism. On the other hand, GT inhibited TNF-α effect. In conclusion, miR-335 serves as a link between inflammation and impaired metabolism in adipose tissue, providing an important mechanistic insight into the molecular basis underlying GT action during obesity.