Prebiotic Fiber Increases Hepatic Acetyl CoA Carboxylase Phosphorylation and Suppresses Glucose-Dependent Insulinotropic Polypeptide Secretion More Effectively When Used with Metformin in Obese Rats

• Published in: The Journal of nutrition Vol. 142; no. 2; pp. 213 - 220
• Main Authors: PYRA, Kim A, SAHA, Dolan C, REIMER, Raylene A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.02.2012
• Subjects: Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Adenylate Kinase - genetics; Adenylate Kinase - metabolism; Animals; Biological and medical sciences; Blood Glucose - metabolism; Body Composition - drug effects; Dietary Fiber - administration & dosage; Dietary Fiber - analysis; Dipeptidyl Peptidase 4 - genetics; Dipeptidyl Peptidase 4 - metabolism; Eating - drug effects; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastric Inhibitory Polypeptide - metabolism; Gastrointestinal Tract - microbiology; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - metabolism; Humans; Hypoglycemic Agents - administration & dosage; Insulin - metabolism; Liver - enzymology; Liver - metabolism; Male; Medical sciences; Metabolic diseases; Metformin - administration & dosage; Obesity; Obesity - chemically induced; Obesity - drug therapy; Obesity - metabolism; Oligosaccharides - administration & dosage; Phosphorylation; Prebiotics; Random Allocation; Rats; Rats, Sprague-Dawley; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Carbon-carbon ligases; Obesity; Phosphorylation; Nutrition; Rat; Digestive system; Enzyme; Secretion; Liver; Rodentia; Nutrition disorder; Vertebrata; Gastrointestinal hormone; Mammalia; Acetyl-CoA carboxylase; Ligases; Animal; Metformin; Gastric inhibitory peptide; Nutritional status
• ISSN: 0022-3166; 1541-6100
• DOI: 10.3945/jn.111.147132

Independently, metformin (MET) and the prebiotic, oligofructose (OFS), have been shown to increase glucagon-like peptide (GLP-1) secretion. Our objective was to determine whether using OFS as an adjunct with MET augments GLP-1 secretion in obese rats. Male, diet-induced obese Sprague Dawley rats were randomized to: 1) high-fat/-sucrose diet [HFHS; control (C); 20% fat, 50% sucrose wt:wt]; 2) HFHS+10% OFS (OFS); 3) HFHS + MET [300 mg/kg/d (MET)]; 4) HFHS+10% OFS+MET (OFS+MET). Body composition, glycemia, satiety hormones, and mechanisms related to dipeptidyl peptidase 4 (DPP4) activity in plasma, hepatic AMP-activated protein kinase (AMPK; Western blots), and gut microbiota (qPCR) were examined. Direct effects of MET and SCFA were examined in human enteroendocrine cells. The interaction between OFS and MET affected fat mass, hepatic TG, secretion of glucose-dependent insulinotropic polypeptide (GIP) and leptin, and AMPKα2 mRNA and phosphorylated acetyl CoA carboxylase (pACC) levels (P < 0.05). Combined, OFS and MET reduced GIP secretion to a greater extent than either treatment alone (P < 0.05). The hepatic pACC level was increased by OFS+MET by at least 50% above all other treatments, which did not differ from each other (P < 0.05). OFS decreased plasma DPP4 activity (P < 0.001). Cecal Bifidobacteria (P < 0.001) were markedly increased and C. leptum decreased (P < 0.001) with OFS consumption. In human enteroendocrine cells, the interaction between MET and SCFA affected GLP-1 secretion (P < 0.04) but was not associated with higher GLP-1 than the highest individual doses. In conclusion, the combined actions of OFS and MET were associated with important interaction effects that have the potential to improve metabolic outcomes associated with obesity.