Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis)leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c),liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of β-oxidation-related genes,such as peroxisome proliferator-activated receptor α (PPAR-α), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid β-oxidation in mice.
Abstract
In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis)leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c),liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of β-oxidation-related genes,such as peroxisome proliferator-activated receptor α (PPAR-α), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid β-oxidation in mice.
참고문헌 (24)
- Fabbrini E, "Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications", Hepatology, 51, pp.679~689 (2010)
- Adiels M, "Overproduction of large VLDL particles is driven by increased liver fat content in man", Diabetologia, 49, pp.755~765 (2006)
- Fabbrini E, "Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity", Proc Natl Acad Sci U S A, 106, pp.15430~15435 (2009)
- Hurjui DM, "The central role of the non alcoholic fatty liver disease in metabolic syndrome", Rev Med Chir Soc Med Nat Iasi, 116, pp.425~431 (2012)
- Yang J, "Pharmacokinetic study of major bioactive components in rats after oral administration of extract of Ilex hainanensis by highperformance liquid chromatography", electrospray ionization mass spectrometry, 2013, pp.77, 21~28
- Afonso MS, "Phenolic compounds from Rosemary (Rosmarinus officinalis L.) attenuate oxidative stress and reduce blood cholesterol concentrations in diet-induced hypercholesterolemic rats", Nutr Metab (Lond), 10, pp.19~ (2013)
- Manoharan S, "Carnosic acid: a potent chemopreventive agent against oral carcinogenesis", Chem Biol Interact, 188, pp.616~622 (2010)
- Mengoni ES, "Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L", Fitoterapia, 82, pp.414~421 (2011)
- Tada M, "Syntheses of carnosic acid and carnosol, anti-oxidants in Rosemary, from pisiferic acid, the major constituent of Sawara", Chem Pharm Bull (Tokyo), 58, pp.27~29 (2010)
- Wang T, "Carnosic acid prevents obesity and hepatic steatosis in ob", ob mice, 2011, pp.41, 87~92
- Kleiner DE, "Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease", Hepatology, 41, pp.1313~1321 (2005)
- Lutz SZ, "Genetic ablation of cGMP-dependent protein kinase type I causes liver inflammation and fasting hyperglycemia", Diabetes, 60, pp.1566~1576 (2011)
- Jang HH, "Black rice (Oryza sativa L.) extract attenuates hepatic steatosis in C57BL", 6 J mice fed a high-fat diet via fatty acid oxidation, 2012, pp.9(27), 1~11[DOI]
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method", Methods, 25, pp.402~408 (2001)
- Roberts R, "Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans", Diabetologia, 52, pp.882~890 (2009)
- Wang XA, "CARD3 deficiency exacerbates diet-induced obesity, hepatosteatosis, and insulin resistance in male mice", Endocrinology, 154, pp.685~697 (2013)
- Polyzos SA, "Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines", Curr Mol Med, 9, pp.299~314 (2009)
- Pettinelli P, "Enhancement in liver SREBP-1c", PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion, 2009, pp.1792, 1080~1086
- Sekiya M, "Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression", Hepatology, 38, pp.1529~1539 (2003)
- Yang ZX, "Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with nonalcoholic fatty liver disease", Hepatol Int, 4, pp.741~748 (2010)
- Liu X, "Stearoyl CoA desaturase 1: role in cellular inflammation and stress", Adv Nutr, 2, pp.15~22 (2011)
- Flowers MT, "Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism", Curr Opin Lipidol, 19, pp.248~256 (2008)
- Higuchi N, "Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease", Exp Ther Med, 2, pp.1077~1081 (2011)
- Nagasawa T, "Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet", Eur J Pharmacol, 536, pp.182~191 (2006)