TY - JOUR TI - The metabolic effects of linoleic acid versus saturated fat in male mice, female mice, and offspring exposed maternally DO - https://doi.org/doi:10.7282/T3W098TN PY - 2017 AB - The obesity epidemic is receiving research attention, but that attention may be targeted incorrectly. The biggest change in American diet during the 20th century was a replacement of saturated and monounsaturated fats with linoleic acid in the form of industrial seed oils. In order to determine whether fatty acid profile is important for producing obesity I fed wild-type C57BL6/J mice high-fat diets with either high concentrations of saturated fat or linoleic acid. In addition to body weight, I performed metabolic assays and collected hypothalamic tissue for measuring gene expression, targeting the mechanism of hypothalamic inflammation. These experimental diets were fed to in males, ovariectomized females with and without estrogen treatment, and to breeder dams to expose their offspring prenatally. I found that in males, linoleic acid contributed to a small but significant increase in body weight compared to saturated fat, but that all high-fat diets produced obese mice. The biggest difference between groups was insulin resistance in the linoleic acid-fed mice. Gene expression evidence of hypothalamic inflammation was unclear. In female mice, estrogen conferred protection from obesity caused by all experimental high-fat diets. Without estrogen, female mice were equally obese from saturated fat and linoleic acid. Glucose metabolism, however, was also impaired by linoleic acid, and expression of hypothalamic genes for metabolism and inflammation were highly variable. In offspring exposed to maternal high-fat diet, females were again protected but not males. Male mice weaned onto a high-fat diet gained more weight when exposed to linoleic acid through maternal feeding than saturated fat. A similar effect on glucose metabolism was seen in male and female offspring as in the first two experiments, where linoleic acid feeding impaired glucose clearance during glucose or insulin challenge. My conclusion is that, in the mouse, linoleic acid is slightly more obesogenic than saturated fat, but effects glucose metabolism much more potently. The effects on obesity, but not glycemia, are partially protected in female mice by estrogen. Due to a lack of clear hypothalamic inflammation biomarkers, these effects are likely occurring in the periphery. KW - Nutritional Sciences KW - Linoleic acid KW - Obesity LA - eng ER -