Studies of UCP2 transgenic and knockout mice reveal that liver UCP2 is not essential for the antiobesity effects of fish oil.
Uncoupling protein 2 (UCP2) is a possible target molecule for energy dissipation. Many dietary fats, including safflower oil and lard, induce obesity in C57BL/6 mice, whereas fish oil does not. Fish oil increases UCP2 expression in hepatocytes and may enhance UCP2 activity by activating the UCP2 molecule or altering the lipid bilayer environment. To examine the role of liver UCP2 in obesity, we created transgenic mice that overexpressed human UCP2 in hepatocytes and examined whether UCP2 transgenic mice showed less obesity when fed a high-fat diet (safflower oil or lard). In addition, we examined whether fish oil had antiobesity effects in UCP2 knockout mice. UCP2 transgenic and wild-type mice fed a high-fat diet (safflower oil or lard) developed obesity to a similar degree. UCP2 knockout and wild-type mice fed fish oil had lower rates of obesity than mice fed safflower oil. Remarkably, safflower oil did not induce obesity in female UCP2 knockout mice, an unexpected phenotype for which we presently have no explanation. However, this unexpected effect was not observed in male UCP2 knockout mice or in UCP2 knockout mice fed a high-lard diet. These data indicate that liver UCP2 is not essential for fish oil-induced decreases in body fat.
Tsuboyama-Kasaoka
Nobuyo
N
Nutritional Science Program, National Institute of Health and Nutrition, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Sano
Kayo
K
Shozawa
Chikako
C
Osaka
Toshimasa
T
Ezaki
Osamu
O
D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use*; D015870:Gene Expression; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000209:etiology / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D012450:Safflower Oil / Q000008:administration & dosage; D012727:Sex Characteristics; D000071246:Uncoupling Protein 2
D019440:Anti-Obesity Agents; D004041:Dietary Fats; D005395:Fish Oils; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D012450:Safflower Oil; C029310:lard