Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.

Obesity is a risk factor for type 2 diabetes in cats. The risk of developing diabetes is severalfold 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 endogenous glucose production (EGP) during the fasted state considering these risk factors. A triple tracer protocol using (2)H(2)O, [U-(13)C(3)]propionate, and [3,4-(13)C(2)]glucose was applied in overnight-fasted cats (12 lean and 12 obese; equal sex distribution) fed three different diets. Compared with lean cats, obese cats had higher insulin (P < 0.001) but similar blood glucose concentrations. EGP was lower in obese cats (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 cats had approximately 1.5 times higher fluxes through phosphoenolpyruvate carboxykinase (P < 0.02) and citrate synthase (P < 0.05) than male obese cats. However, GNG was not higher because pyruvate cycling was increased 1.5-fold (P < 0.03). These results support the notion that fasted obese cats have lower hepatic EGP compared with lean cats and are still capable of maintaining fasting euglycemia, despite the well-documented existence of peripheral insulin resistance in obese cats. Our data further suggest that sex-related differences exist in the regulation of hepatic glucose metabolism in obese cats, 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.

To determine the effectiveness of dietary lysine supplementation in cats with enzootic upper respiratory disease (URD), 50 cats were fed a ration containing 11 or 51 g lysine/kg diet for 52 days. Food intake, body weight, clinical signs, plasma amino acid concentrations and presence of Chlamydophila felis or feline herpesvirus (FHV)-1 DNA within the conjunctival fornix were assessed. Food and lysine intake of both dietary groups decreased between days 17 and 22, coinciding with peak disease and viral presence. Mean disease score for cats fed the supplemented ration (0.94) was higher than for those fed the basal diet (0.21); however, this could be attributed to a small subset of male cats which demonstrated fighting behavior that may have contributed to stress within that cage. FHV-1 DNA was detected on 12 occasions in six cats receiving the supplemented diet and on one occasion in one cat fed the basal diet. C felis DNA was never detected. Mean plasma arginine concentration was lower and plasma lysine concentration was higher in supplemented cats. Mean plasma arginine concentration declined throughout the study in both dietary groups. Data from the present study raise important questions but do not permit a definitive conclusion regarding the efficacy of dietary lysine supplementation in cats with enzootic URD.

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. Effect of macronutrients, age, and obesity on 6-and 24-h postprandial glucose metabolism in cats. Am J Physiol Regul Integr Comp Physiol 301: R1798 -R1807, 2011. First published September 21, 2011 doi:10.1152/ajpregu.00342.2011.-Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer-2 H2O, [U-13 C3] propionate, and [3,4-13 C2] glucose infusion, and indirect calorimetry-we investigated carbohydrate and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12 old lean, and 12 old obese), each fed three different diets (high protein with and without polyunsaturated fatty acids, and high carbohydrate) in a crossover design. EGP was lowest in fasted and postprandial obese cats despite peripheral insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most important pathway for EGP in all groups, but glycogen contributed significantly. Insulin and leptin concentrations were higher in old than in young lean cats; adiponectin was lowest in obese cats but surprisingly highest in lean old cats. Diet had little effect on metabolic parameters. We conclude that hepatorenal insulin resistance does not develop in the fasted or postprandial state, even in long-term obese cats, allowing the maintenance of euglycemia through lowering EGP. Glycogen plays a major role in EGP, especially in lean fasted cats, and in the postprandial state. Aging may predispose to insulin resistance, which is a risk factor for diabetes in cats. Mechanisms underlying the high adiponectin of healthy old lean cats need to be further explored. nuclear magnetic resonance spectroscopy; adipocytokines; indirect calorimetry; glycogenolysis; insulin resistance; endogenous glucose production IN MAN AND IN CATS, obesity and age are factors in the development of diabetes (8, 69). As in people, the incidence of feline obesity and diabetes has increased dramatically in the past 3 decades (2,8). Obesity is now the most common nutritional disorder in cats, and diabetes is one of the most common endocrinopathies in aging cats. Little is known about the metabolic changes in obese cats and the influence of age and food intake on metabolic parameters that contribute to increasing obesity and diabetes.Cats are obligatory carnivores that naturally subsist on a high-protein and high-fat diet. It has been stated anecdotally that glycogen contributes less to glucose production in cats than other species. Rogers et al. (61) reported that cats cannot readily adapt their sources of glucose production, a notion that has been refuted by others (25,26,65,66). We have previously shown that, in fasted cats, fractional gluconeogenesis (GNG) and glycogenolysis is similar to hum...