title: Supplementation of a high-fat diet with chlorogenic acid is associated with insulin resistance and hepatic lipid accumulation in mice.
abstract: 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.
authors.affiliation: School of Plant Biology, and the Institute of Agriculture, University of Western Australia, Crawley, Western Australia 6009, Australia.
authors.forename: Aidilla
authors.initials: A
authors.lastname: Mubarak
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hodgson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Considine
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Vance B
authors.initials: VB
authors.lastname: Matthews
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D018149:Glucose Intolerance / Q000209:etiology; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy / Q000209:etiology; D010766:Phosphorylation; D059808:Polyphenols / Q000008:administration & dosage
chemical_list: D059808:Polyphenols; D002726:Chlorogenic Acid; D055372:AMP-Activated Protein Kinases