During the development of obesity, adipose tissue undergoes major expansion and remodeling, but the biological processes involved in this transition are not well understood. The objective of this study was to analyze global gene expression profiles of adipose tissue in dogs, fed a high-fat diet, during the transition from a lean to obese phenotype. Nine female beagles (4.09 ± 0.64 yr; 8.48 ± 0.35 kg) were randomized to ad libitum feeding or body weight maintenance. Subcutaneous adipose tissue biopsy, blood, and dual x-ray absorptiometry measurements were collected at 0, 4, 8, 12, and 24 wk of feeding. Serum was analyzed for glucose, insulin, fructosamine, triglycerides, free fatty acids, adiponectin, and leptin. Formalin-fixed adipose tissue was used for determination of adipocyte size. Adipose RNA samples were hybridized to Affymetrix Canine 2.0 microarrays. Statistical analysis, using repeated-measures ANOVA, showed ad libitum feeding increased (P < 0.05) body weight (0 wk, 8.36 ± 0.34 kg; 24 wk, 14.64 ± 0.34 kg), body fat mass (0 wk, 1.36 ± 0.24 kg; 24 wk, 6.52 ± 0.24 kg), adipocyte size (0 wk, 114.66 ± 17.38 μm(2); 24 wk, 320.97 ± 0.18.17 μm(2)), and leptin (0 wk, 0.8 ± 1.0 ng/ml; 24 wk, 12.9 ± 1.0 ng/ml). Microarrays displayed 1,665 differentially expressed genes in adipose tissue as weight increased. Alterations were seen in adipose tissue homeostatic processes including metabolism, oxidative stress, mitochondrial homeostasis, and extracellular matrix. Adipose transcriptome changes highlight the dynamic and adaptive response to ad libitum feeding and obesity development.
Background: Insulin detemir and insulin glargine are synthetic long-acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time-action profile, while insulin detemir has significantly less within-subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events.Objectives: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. Animals: Ten young, healthy, neutered, purpose-bred cats. Methods: Randomized, cross-over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection.Results: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8 AE 0.8 and 1.3 AE 0.5 hours for insulin detemir and insulin glargine, respectively, P 5 .03). End of action of insulin detemir was reached at 13.5 AE 3.5 hours and for insulin glargine at 11.3 AE 4.5 hours (P 5 .18). Time-to-peak action of insulin detemir was reached at 6.9 AE 3.1 hours and for insulin glargine at 5.3 AE 3.8 hours (P 5 .7). The time-action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others.Conclusion and Clinical Importance: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once-a-day drugs. Peak effects of both insulin analogs are pronounced in some cats.
Identifying dietary effects on appetite-regulating hormones will enhance our understanding of appetite control. Before complex diets are tested, effects of specific macronutrients or feeding frequency should be identified. The objectives of this nutrition study were to identify differences in endocrine response with feeding frequency (Exp. 1) and after a single dose of a sole macronutrient (Exp. 2). A control diet supplying similar energy content from carbohydrate, protein, and fat was fed to maintain ideal BW. In Exp. 1, 8 healthy adult (1.9 ± 0.1 yr old) female hound cross dogs with an average BW of 22 kg (4.8 ± 0.8 BCS based on a 9-point scale) were randomly allotted to 1 of 2 treatments (fed once or twice daily) in a crossover design. After a 14-d adaptation period, a blood sample was taken (10 mL) before feeding, and samples were collected every 2 h postprandially for 24 h. In Exp. 2, dogs were randomly allotted to 1 of 4 treatments in a 4 × 4 Latin square design. After a 6-d adaptation period, the normal meal on d 7 was replaced with a bolus of maltodextrin (50 g in water; CARB), canned chicken (50 g; PROT), lard (25 g; fat), or water (200 mL). A blood sample (10 mL) was taken at 0, 30, 60, 90, 120, 150, 180, 240, 300, and 360 min postprandial. Total ghrelin, active glucagon-like peptide-1 (GLP-1), insulin, and glucose concentrations were measured. Data were analyzed to compare changes from baseline and area under the curve (AUC) among treatments. In Exp. 1, all hormones were quite variable throughout the day, with a few insulin and GLP-1 differences because of feeding frequency. In Exp. 2, CARB produced a marked peak in glucose and insulin concentrations compared with PROT, fat, or water, resulting in increased glucose (P < 0.001) and insulin (P = 0.07) incremental AUC values. On the other hand, the fat treatment led to increased GLP-1 concentrations over time. Ghrelin AUC was not different among treatments. The circulating hormone data were highly variable and indicate that diet plays a role in insulin and GLP-1 secretion, but more research is required to elucidate these effects.
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