Supplementation of a high-fat diet with chlorogenic acid is associated with insulin resistance and hepatic lipid accumulation in mice.

The increasing prevalence of the metabolic syndrome requires a greater need for therapeutic and prevention strategies. Higher coffee consumption is consistently associated with a lower risk of type 2 diabetes in population studies. Dietary polyphenols have been linked to benefits on several features of the metabolic syndrome. Chlorogenic acid (CGA), a major component of coffee, is one of the most consumed polyphenols in the diet. In our study, we conducted a controlled dietary intervention over 12 weeks in male mice. There were three dietary groups: (i) normal diet, (ii) high-fat diet, and (iii) high-fat diet + CGA. We assessed the effect of CGA at a physiologically obtainable dose (1 g/kg of diet) on high-fat-diet-induced obesity, glucose intolerance, insulin resistance, and also fatty acid oxidation and insulin signaling in C57BL/6 male mice. Supplementation of CGA in the high-fat diet did not reduce body weight compared to mice fed the high-fat diet alone (p = 0.32). CGA resulted in increased insulin resistance compared to mice fed a high-fat diet only (p < 0.05). CGA resulted in decreased phosphorylation of AMP-activated protein kinase (AMPK) (p < 0.001) and acetyl carboxylase β (ACCβ), a downstream target of AMPK (p < 0.05), in liver. The liver of mice fed a high-fat diet supplemented with CGA had a higher lipid content (p < 0.05) and more steatosis relative to mice fed a high-fat diet only, indicating impaired fatty acid oxidation. This study suggests that CGA supplementation in a high-fat diet does not protect against features of the metabolic syndrome in diet-induced obese mice.