Submitted on September 15, 2008
Revised on January 22, 2009
Accepted on January 27, 2009
The impact of obesity, gender and diet on hepatic glucose production in cats
Saskia Kley1, Margarethe HOENIG2*, John Glushka3, Eunsook S Jin4, Shawn C Burgess4, Mark Waldron5, Erin T. Jordan6, James H. Prestegard3, Duncan C. Ferguson7, Shaoxiong Wu8, and Darin E. Olson9
1 Royal Veterinary College, University of London
2 University of Illinois
3 University of Georgia, Athens, Georgia
4 University of Texas Southwestern Medical Center
5 4Nestle Purina Research, Lausanne, Switzerland
6 University of Georgia
7 University of Illinois College of Veterinary Medicine, Urban-Champaign, IL
8 Emory University, Atlanta, Georgia,
9 Emory University School of Medicine and the Atlanta VAMC, Atlanta, Georgia, USA
* To whom correspondence should be addressed. E-mail: mhoenig{at}uiuc.edu.
Obesity is a risk factor for type 2 diabetes in cats. The risk of developing diabetes is several-fold greater for male cats than for females, even after having been neutered early in life. The purpose of this study was to investigate the role of different metabolic pathways in the regulation of EGP during the fasted state considering these risk factors. A triple tracer protocol using 2H2O, [U-13C3] propionate, and [3,4-13C2] glucose was applied in overnight-fasted cats (12 lean and 12 obese ; equal gender distribution) fed 3 different diets. Compared to LEAN, OBESE had higher insulin (p < 0.001) but similar blood glucose concentrations. Endogenous glucose production (EGP) was lower in OBESE (p<0.001) due to lower glycogenolysis and gluconeogenesis (GNG; p<0.03). Insulin, body mass index and girth correlated negatively with EGP (p< 0.003). Female OBESE had approximately 1.5 times higher fluxes through phosphoenolpyruvate carboxykinase (p <0.02) and citrate synthase (p < 0.05) than male OBESE. However, GNG was not higher because pyruvate cycling was increased 1.5-fold (p < 0.03). These results support the notion that fasted OBESE have lower hepatic EGP compared to LEAN and are still capable to maintain fasting euglycemia, despite the well documented existence of peripheral insulin resistance in OBESE. Our data further suggest that gender differences exist in the regulation of hepatic glucose metabolism in OBESE suggesting that pyruvate cycling acts as a controlling mechanism to modulate EGP. Increased pyruvate cycling could therefore be an important factor in modulating the diabetes risk in female cats.
