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Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression.
Hepatology. 2003 Dec; 38(6):1529-39.Hep

Abstract

Leptin-deficient ob/ob mice show many characteristics of obesity, including excess peripheral adiposity as well as severe hepatic steatosis, at least in part, due to increased hepatic lipogenesis. Polyunsaturated fatty acids (PUFAs) are not only ligands for peroxisome proliferator-activated receptor (PPAR) alpha but are also negative regulators of hepatic lipogenesis, which is thought to be mediated by the repression of sterol regulatory element-binding protein (SREBP)-1. We have previously shown that the disruption of SREBP-1 in ob/ob mice decreased their liver triglyceride storage. To examine whether PUFAs could reduce hepatic triglyceride deposition, we challenged ob/ob mice with dietary PUFA. It is demonstrated that PUFA markedly decreased the mature form of SREBP-1 protein and thereby reduced the expression of lipogenic genes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) in the livers of ob/ob mice. Consequently, the liver triglyceride content and plasma alanine aminotransferase (ALT) levels were decreased. Furthermore, both hyperglycemia and hyperinsulinemia in ob/ob mice were improved by PUFA administration, similar to the effect of PPARalpha activators. In conclusion, PUFAs ameliorate obesity-associated symptoms, such as hepatic steatosis and insulin resistance, presumably through both down-regulation of SREBP-1 and activation of PPARalpha.

Authors+Show Affiliations

Department of Internal Medicine, Tokyo University Graduate School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14647064

Citation

Sekiya, Motohiro, et al. "Polyunsaturated Fatty Acids Ameliorate Hepatic Steatosis in Obese Mice By SREBP-1 Suppression." Hepatology (Baltimore, Md.), vol. 38, no. 6, 2003, pp. 1529-39.
Sekiya M, Yahagi N, Matsuzaka T, et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology. 2003;38(6):1529-39.
Sekiya, M., Yahagi, N., Matsuzaka, T., Najima, Y., Nakakuki, M., Nagai, R., Ishibashi, S., Osuga, J., Yamada, N., & Shimano, H. (2003). Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology (Baltimore, Md.), 38(6), 1529-39.
Sekiya M, et al. Polyunsaturated Fatty Acids Ameliorate Hepatic Steatosis in Obese Mice By SREBP-1 Suppression. Hepatology. 2003;38(6):1529-39. PubMed PMID: 14647064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. AU - Sekiya,Motohiro, AU - Yahagi,Naoya, AU - Matsuzaka,Takashi, AU - Najima,Yuho, AU - Nakakuki,Masanori, AU - Nagai,Ryozo, AU - Ishibashi,Shun, AU - Osuga,Jun-ichi, AU - Yamada,Nobuhiro, AU - Shimano,Hitoshi, PY - 2003/12/4/pubmed PY - 2003/12/19/medline PY - 2003/12/4/entrez SP - 1529 EP - 39 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 38 IS - 6 N2 - Leptin-deficient ob/ob mice show many characteristics of obesity, including excess peripheral adiposity as well as severe hepatic steatosis, at least in part, due to increased hepatic lipogenesis. Polyunsaturated fatty acids (PUFAs) are not only ligands for peroxisome proliferator-activated receptor (PPAR) alpha but are also negative regulators of hepatic lipogenesis, which is thought to be mediated by the repression of sterol regulatory element-binding protein (SREBP)-1. We have previously shown that the disruption of SREBP-1 in ob/ob mice decreased their liver triglyceride storage. To examine whether PUFAs could reduce hepatic triglyceride deposition, we challenged ob/ob mice with dietary PUFA. It is demonstrated that PUFA markedly decreased the mature form of SREBP-1 protein and thereby reduced the expression of lipogenic genes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) in the livers of ob/ob mice. Consequently, the liver triglyceride content and plasma alanine aminotransferase (ALT) levels were decreased. Furthermore, both hyperglycemia and hyperinsulinemia in ob/ob mice were improved by PUFA administration, similar to the effect of PPARalpha activators. In conclusion, PUFAs ameliorate obesity-associated symptoms, such as hepatic steatosis and insulin resistance, presumably through both down-regulation of SREBP-1 and activation of PPARalpha. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/14647064/Polyunsaturated_fatty_acids_ameliorate_hepatic_steatosis_in_obese_mice_by_SREBP_1_suppression_ DB - PRIME DP - Unbound Medicine ER -