Research Article Details

Article ID: A26737
PMID: 19875987
Source: Obesity (Silver Spring)
Title: Decreased liver fatty acid delta-6 and delta-5 desaturase activity in obese patients.
Abstract: Steatosis in obese nonalcoholic fatty liver disease (NAFLD) patients is a clinicopathological condition associated with depletion of n-3 polyunsaturated fatty acids (PUFA), a feature that may be related to PUFA desaturation. Liver Delta-6 and Delta-5 desaturase (Delta-6D and Delta-5D) activities, homeostasis model assessment of insulin resistance (HOMA(IR)), and ferric reducing ability of plasma (FRAP) were evaluated in 13 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 15 nonobese patients who underwent laparoscopic cholecystectomy (controls). Liver Delta-6D and Delta-5D activities in obese patients were 87% and 66% lower than controls (P < 0.001), respectively, with a 62% diminution in the Delta-6D/Delta-5D activity ratio (P < 0.02). Delta-6D inversely correlated with both HOMA(IR) (r = -0.70, P < 0.0001) and oxidative stress assessed as the reciprocal value of FRAP (r = -0.40, P < 0.05). Delta-5D negatively correlated with HOMA(IR) (r = -0.48, P < 0.01) but not with FRAP(-1) (r = -0.13, not significant). In conclusion, liver PUFA desaturation is diminished in obese NAFLD patients, in association with underlying insulin resistance and oxidative stress, which may play a role in altering lipid metabolism favoring fatty infiltration.
DOI: 10.1038/oby.2009.379

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details
S02 Enhance lipid metabolism triglyceride-lowering; lipid tolerance; lipid metabolism 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; Details
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I14 9970 Obesity An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D248 Obeticholic Acid Chemical drug DB05990 NR1H4 activator; NR1H4 agonist; FXR agonist Enhance lipid metabolism Approval rejected Details
D504 Polyunsaturated Fatty Acids Supplement -- -- -- Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details