title: Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis.
abstract: The hormonal mediators of obesity-induced insulin resistance and compensatory hyperinsulinemia in dogs have not been identified. Plasma samples were obtained after a 24-h fast from 104 client-owned lean, overweight, and obese dogs. Plasma glucose and insulin concentrations were used to calculate insulin sensitivity and β-cell function with the use of the homeostasis model assessment (HOMA(insulin sensitivity) and HOMA(β-cell function), respectively). Path analysis with multivariable linear regression was used to identify whether fasting plasma leptin, adiponectin, or glucagon-like peptide-1 concentrations were associated with adiposity, insulin sensitivity, and basal insulin secretion. None of the dogs were hyperglycemic. In the final path model, adiposity was positively associated with leptin (P < 0.01) and glucagon-like peptide-1 (P = 0.04) concentrations. No significant total effect of adiposity on adiponectin in dogs (P = 0.24) was observed. If there is a direct effect of leptin on adiponectin, then our results indicate that this is a positive relationship, which at least partly counters a negative direct relationship between adiposity and adiponectin. Fasting plasma leptin concentration was directly negatively associated with fasting insulin sensitivity (P = 0.01) and positively associated with β-cell function (P < 0.01), but no direct association was observed between adiponectin concentration and either insulin sensitivity or β-cell function (P = 0.42 and 0.11, respectively). We conclude that dogs compensate effectively for obesity-induced insulin resistance. Fasting plasma leptin concentrations appear to be associated with obesity-associated changes in insulin sensitivity and compensatory hyperinsulinemia in naturally occurring obese dogs. Adiponectin does not appear to be involved in the pathophysiology of obesity-associated changes in insulin sensitivity.
authors.affiliation: Centre for Companion Animal Health, School of Veterinary Science, The University of Queensland, Brisbane, Australia. k.verkest@uq.edu.au
authors.forename: K R
authors.initials: KR
authors.lastname: Verkest
authors.forename: L M
authors.initials: LM
authors.lastname: Fleeman
authors.forename: J M
authors.initials: JM
authors.lastname: Morton
authors.forename: K
authors.initials: K
authors.lastname: Ishioka
authors.forename: J S
authors.initials: JS
authors.lastname: Rand
mesh_terms: D052242:Adiponectin / Q000097:blood*; D050154:Adiposity / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D005215:Fasting; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology; D020738:Leptin / Q000097:blood*; D009765:Obesity / Q000503:physiopathology / Q000662:veterinary*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D052216:Glucagon-Like Peptide 1