Adiponectin signaling is essential to thermogenic effects of polyphenol-rich green tea extract

Nowadays obesity is a challenge for the health system worldwide as it is a risk factor for a huge range of diseases with high comorbidity. Directly related to sedentary lifestyle and food imbalance due to the ingestion of hypercaloric foods with reduced nutrient content, the number of people with obesity and overweight has been increasing in the last decades. Adipose tissue (AT) is widely associated with obesity because it acts as a regulator of metabolic homeostasis and body thermoregulation. AT can be classified as white adipose tissue (WAT) and brown adipose tissue (BAT). BAT is characterized by the presence of numerous lipid droplets and expression of the uncoupling protein 1 (UCP-1), whose main function is to promote non-shivering thermogenesis. WAT cells have an as main function to store energy in the form of triglycerides (lipogenesis) and release their stocks when performing lipolysis. Recently, a variation of WAT, called beige/"brite" adipocytes was discovered. These adipocytes have some characteristics of brown adipocytes once they express UCP-1 and perform thermogenesis with consequent energy expenditure. The subcutaneous WAT undergoes this variation to beige by different stimuli, in a process called browning. Adiponectin plays an important role in inducing browning in the subcutaneous WAT and data from our research group showed that levels of adiponectin that was reduced in the plasma of obese mice were restored when exposed to the green tea (GT) treatment as well as GT increased beige cells. To investigate the mechanisms involved, our general objective was to verify in vivo the role of adiponectin by using knockout mice (AdipoKO) exposed to a high-fat diet (HFD) and treated with GT. For this purpose, the animals received high-fat diet (HFD) for 8 weeks and after that period we started gavage with GT extract (500 mg/kg) for 12 weeks in addition to the hyperlipidic diet. Our findings indicate that treatment with GT reversed complication of obesity in wild-type mice by decreasing final weight gain, adiposity index, adipocyte size and insulin resistance (IR). However, the action of the GT was not effective in reversing these markers in the AdipoKO animals, although the treatment acts independently to reverse the IR process. In addition, GT treatment also induced thermogenic activation of BAT and promoted phenotypic alteration of WAT dependent on adiponectin once it showed up to be not effective in inducing thermogenic genes in the subcutaneous WAT of AdipoKO mice. These findings suggest that treatment with GT modulates some features of obesity such as weight gain, adiposity index and hypertrophy of adipocytes as well as induces the differentiation of white adipocytes to beige cells, in addition to activation of BAT thermogenesis and higher energy expenditure, dependent on adiponectin. Thus, we contribute in this study indicating that GT actions on browning induction depend on adiponectin.

Financial support: Fapesp 2016/12059-8; 2017/10531-4