Characterization of Adiponectin in the Canine
Type of DegreeDissertation
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Obesity is the most common nutritional disorder observed in small animal medicine. Obesity in dogs can result in numerous complications, including traumatic and degenerative orthopedic diseases, cardiopulmonary compromise, heat and exercise intolerance, pancreatitis, glucose intolerance, and diabetes mellitus. Adiponectin is a 30 kD hormone produced exclusively by adipocytes that was identified independently by four different groups in 1995. Serum concentrations of adiponectin are high in the normal state, accounting for approximately 0.01-0.03% of total plasma proteins. However, circulating concentrations of this hormone are significantly reduced in obesity, insulin resistance and diabetes. Decreased adiponectin concentrations have been significantly correlated with the development of insulin resistance. Insulin resistance is often associated with obesity and may be one of the links between increased adiposity and the development of type 2 diabetes. In dogs, the impact of compromised glucose tolerance and insulin resistance on health appears when dogs are even moderately overweight. The reduced capability to absorb glucose can hinder the ability of organs, tissues, and body systems to function properly, which can result in chronic health conditions. With increasing evidence that adiponectin may physiologically regulate energy metabolism and its importance in the relationship between obesity and the development of insulin resistance, adioponectin could potentially serve as a treatment target or marker for obesity, insulin resistance, and/or pre-diabetes. In order to determine the effects that insulin resistance has on adiponectin secretion and expression we have first characterized the secretion, circulating protein complex profile, and gene expression in normal dogs. Adiponectin is secreted into the serum as a >360 kD multimer, termed the HMW (high molecular weight) complex and as a 180 kD LMW (low molecular weight) complex. Under various reducing and denaturing conditions, adiponectin separates into cross-linked products whose molecular sizes are multiples of 30 kD. Additionally, gene expression of adiponectin is observed within visceral adipose tissue. We next studied adiponectin gene expression and protein secretion in dogs fed a high-fat diet in order to induce adiposity. High-fat fed dogs had a 2.6 fold increase in adiposity in the face of minimal weight gain (15.4%). High-fat fed dogs developed high/normal fasting insulin concentrations compared to controls at the peak of adiposity. Interestingly, adiponectin gene expression and secretion of total and high molecular weight adiponectin were unaffected at all timepoints during the course of this study.