Arsenic exposure through drinking water is a public health problem that affects more than 300 million people worldwide in more than 70 countries. Arsenic has been recognized as a risk factor for type 2 diabetes with specific mechanisms of action, however it is still uncertain whether arsenic is also an obesogen. Chronic high-calorie diet intake seems to be the most important risk factor leading to obesity. Some evidence suggests that diet can modulate, positively or negatively, the effects of environmental pollutants and chemicals, including arsenic. Thus, in order to combine the effects of different environmental risk factors, the present study evaluates the effects of arsenic on the endocrine and lipolytic metabolism of adipose tissue (AT)/adipocytes on its own or in combination with high-fat saturated diet (HFSD) in C57BL/6 mice or in the presence of elevated palmitic acid concentrations in 3T3-L1 mature adipocytes. Serum leptin and adiponectin in mice were increased or decreased, respectively in response to HFSD, without an influence of the 8-wk arsenic exposure (100 μg/L). However, adiponectin gene expression decreased by arsenic in subcutaneous AT and the effect was potentiated by HFSD in retroperitoneal AT. Whereas, leptin expression was increased by arsenic and potentiated by HFSD in epididymal AT. In vitro leptin secretion was significantly decreased by 75% in response to arsenic (1 μM) and in a lower extend when combined with palmitic acid (200 μM) (25%) in 3T3-L1 adipocytes exposed for 72 h. Nevertheless, leptin gene expression was decreased in both conditions 50%. Adiponectin synthesis and secretion in 3T3-L1 adipocytes was decreased 25% by arsenic with or without palmitic acid. Fasting serum free fatty acids in mice were reduced 50% by arsenic, HFSD or both. In 3T3-L1 adipocytes, arsenic treatment induced basal lipolysis by 50%, nonetheless a 3-fold induction was observed when combined with palmitic acid. Contrary, stimulated lipolysis was impaired by 50% only with arsenic exposure. Thus, our combined in vivo and in vitro results show that arsenic alters endocrine and lipolytic AT metabolism, and that the effect can be negatively modulated by HFSD, propitiating obesity-associated metabolic disorders.

Arsenic impairs endocrine and lipolytic adipose tissue metabolism and it is modulated by high-fat saturated diet

256th National Meeting (2018)

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