Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: Correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1792

Article

Pettinelli, Paulina¹  del Pozo, Talia²  Araya, Julia³  Rodrigo, Ramon¹  Veronica Araya, A.⁴  Smok, Gladys⁵  Csendes, Attila⁶  Gutierrez, Luis⁶  Rojas, Jorge⁶  Korn, Owen⁶  Maluenda, Fernando⁶  Diaz, Juan C.⁶  Rencoret, Guillermo⁶  Braghetto, Italo⁶  Castillo, Jaime⁶  Poniachik, Jaime⁷  Videla, Luis A.¹ 

[1] Univ Chile, Programa Farmacol Mol & Clin, Inst Ciencias Biomed, Fac Med, Santiago 7, Chile

[2] Univ Chile, Lab Bioinformat & Gene Express, Inst Nutr & Food Technol, Santiago 7, Chile

[3] Univ Chile, Fac Med, Dept Nutr, Santiago 7, Chile

[4] Univ Chile, Clin Hosp, Dept Endocrinol, Santiago 7, Chile

[5] Univ Chile, Clin Hosp, Dept Pathol Anat, Santiago 7, Chile

[6] Univ Chile, Clin Hosp, Dept Surg, Santiago 7, Chile

[7] Univ Chile, Clin Hosp, Dept Med, Santiago 7, Chile

关键词: Obesity;    Liver steatosis;    Sterol receptor element binding protein-1c;    Peroxisome proliferator activated receptor-alpha;    Insulin resistance;   

DOI  :  10.1016/j.bbadis.2009.08.015

来源: Elsevier

【 摘 要 】

Sterol receptor element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) mRNA expression was assessed in liver as signaling mechanisms associated with steatosis in obese patients. Liver SREBP-1c and PPAR-alpha mRNA (RT-PCR), fatty acid synthase (FAS) and carnitine palmitoyltransferase-1a (CPT-1a) mRNA (real-time RT-PCR), and n-3 long-chain polyunsaturated fatty acid (LCPUFA)(GLC) contents, plasma adiponectin levels (RIA), and insulin resistance (IR) evolution (HOMA) were evaluated in 11 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 8 non-obese subjects who underwent laparoscopic cholecystectomy (controls). Liver SREBP-1c and FAS mRNA levels were 33% and 70% higher than control values (P<0.05), respectively. whereas those of PPAR-alpha and CPT-1a were 16% and 65% lower (P<0.05), respectively, with a significant 62% enhancement in the SREBP-1c/PPAR-alpha ratio. Liver n-3 LCPUFA levels were 53% lower in obese patients who also showed IR and hipoadiponectinemia over controls (P<0.05). IR negatively correlated with both the hepatic content of n-3 LCPUFA (r = -0.55; P<0.01) and the plasma levels of adiponectin (r = -0.62; P<0.005). Liver SREBP-1c/PPAR-alpha ratio and n-3 LCPUFA showed a negative correlation (r = -0.48; P<0.02) and positive associations with either HOMA (r = 0.75; P<0.0001) or serum insulin levels (r = 0.69; P<0.001). In conclusion, liver up-regulation of SREBP-1c and down-regulation of PPAR-alpha occur in obese patients, with enhancement in the SREBP-1c/PPAR-alpha ratio associated with n-3 LCPUFA depletion and K a condition that may favor lipogenesis over FA oxidation thereby leading to steatosis. (C) 2009 Elsevier B.V. All rights reserved.

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