Obo, T.; Hashiguchi, H.; Matsuda, E.; Kawade, S.; Ogiso, K.; Iwai, H.; Ataka, K.; Yasuda, O.; Arimura, A.; Deguchi, T.; Asakawa, A.; Nishio, Y.

Aims/Introduction: The {omega}3 polyunsaturated fatty acids in fish oil enhance heat production in adipocytes and exert anti-obesity effects, but the effects of fish oil on heat production in diet-induced obese (DIO) mice are unclear. In this study, we examined whether diets containing fish oil increased the expression of heat-producing genes in adipose tissue and increased body temperature in DIO mice, resulting in weight loss. We also examined fibroblast growth factor 21 (FGF21) levels in blood and the expression of the FGF21 gene in adipose tissue of DIO mice fed fish oil. Materials and Methods: C57BL6/J mice were fed a lard-based high-fat diet for 8 weeks starting at 5 weeks of age and then divided into two groups: one group was fed a fish oil-based high-fat diet, and the other group was fed a lard-based high-fat diet continuously for another 8 weeks. Mice fed a control diet for 16 weeks from the age of 5 weeks served as the control group. Mice were dissected at 21 weeks and used for analysis. Results: Mice fed a fish oil-based high-fat diet lost body weight gain, adipose tissue weight gain, and reduced insulin/leptin resistance. In addition, the rectal temperatures of mice fed a fish oil-based high-fat diet remained higher. The administration of fish oil increased the expression of heat-producing genes in brown adipose tissue (BAT) but did not alter heat-producing genes in inguinal white adipose tissue (WAT). In DIO mice fed a fish oil-based high-fat diet, the FGF21 expression in BAT increased. Furthermore, {beta}klotho expression in BAT increased and the blood FGF21 concentration was decreased compared to mice fed a lard-based high-fat diet. Conclusions: In DIO mice, fish oil was shown to increase rectal temperature and ameliorate obesity. Furthermore, fish oil enhanced heat production in BAT, but not WAT, in DIO mice.