Obesity-associated hepatic
lipid accumulation and chronic low-grade
inflammation lead to metabolic defects.
Saturated fatty acids (SFA) are a risk factor for, whereas
unsaturated fatty acids (UFA) are thought to be protective against, developing
metabolic diseases. Sex differences exist in the regulation of metabolism. We tested the hypothesis that diets high in SFA, mono-UFA (MUFA), or poly-UFA (PUFA) had early, sex-distinct effects that differentially contribute to long-term metabolic disturbance such as
fatty liver and
insulin resistance. Metabolic changes including body and fat mass, circulating
leptin and
glucose levels, plasma
lipid profile, hepatic
lipid accumulation, expression levels of genes related to lipid metabolism and low-grade
inflammation, and tissue
insulin sensitivity were compared between male and female mice fed with a low-fat chow, or high-fat SFA, MUFA, or PUFA for a short period of four days. SFA and MUFA males increased adiposity associated with increased liver
lipid accumulation and rapid activation of
inflammation in adipose and muscle tissues, whereas PUFA males did not show
lipid accumulation or tissue
inflammation compared to chow males. All SFA and UFA males displayed tissue
insulin resistance. In contrast, female high-fat diet groups had normal liver
lipid content and maintained tissue
insulin sensitivity without showing tissue
inflammation. Therefore, sex differences existed during early phase of development of metabolic dysfunction. The beneficial effects of PUFA, but not MUFA, were corroborated in protection of
obesity,
hyperlipidemia,
fatty liver, and low-grade
inflammation. The benefit of MUFA and PUFA in maintaining tissue
insulin sensitivity in males, however, was questioned.