title: Changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis induced by an acetyl-L-carnitine and nicotinamide treatment in dyslipidaemic insulin-resistant rats.
abstract: Normal rats fed a sucrose-rich diet (SRD) develop dyslipidaemia and insulin resistance. The present study examined whether administration of the mitochondrial nutrients nicotinamide and acetyl-L-carnitine reversed or improved these metabolic abnormalities. Male Wistar rats were fed an SRD for 90 days. Half the rats then received daily injections of nicotinamide (25 mg/kg, i.p.) and acetyl-L-carnitine (50 mg/kg, i.p.) for a further 90 days. The remaining rats in the SRD-fed group and those in a normal chow-fed control group were injected with an equal volume of saline solution for the same period. The following parameters were determined in all groups: (i) liver activity of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and carnitine-palmitoyl transferase-1 (CPT-1); (ii) hepatic and skeletal muscle triacylglycerol content, plasma glucose, insulin, free fatty acid (FFA) and triacylglycerol levels and pancreatic insulin content; and (iii) glucose tolerance. Administration of nicotinamide and acetyl-L-carnitine to the SRD-fed rats reduced dyslipidaemia, liver steatosis, muscle triacylglycerol content and hepatic FAS and ACC activities and increased CPT-1 activity. In addition nicotinamide and acetyl-L-carnitine improved the glucose disappearance rate (K(g)), normalized plasma glucose levels and moderately increased insulinaemia without altering pancreatic insulin content. Finally, nicotinamide and acetyl-l-carnitine administration reduced bodyweight gain and visceral adiposity. The results of the present study suggest that altering key hepatic lipogenic and fatty acid oxidative enzymatic activity could improve dyslipidaemia, liver steatosis and visceral adiposity. Indeed, administration of nicotinamide and acetyl-l-carnitine improved glucose intolerance and normalized plasma glucose levels.
authors.affiliation: Department of Biochemistry, School of Biochemistry, Litoral University, Santa Fe, Argentina.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Ferreira
authors.forename: Maria del C
authors.initials: Mdel C
authors.lastname: Camberos
authors.forename: Dante
authors.initials: D
authors.lastname: Selenscig
authors.forename: Lucía C
authors.initials: LC
authors.lastname: Martucci
authors.forename: Adriana
authors.initials: A
authors.lastname: Chicco
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: Lombardo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cresto
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000108:Acetylcarnitine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D050171:Dyslipidemias / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002149:Energy Intake / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
chemical_list: D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D009536:Niacinamide; D000108:Acetylcarnitine; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose