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University of California Davis, Davis, CA
3To whom correspondence should be addressed. E-mail: rcbackus{at}ucdavis.edu.
KEY WORDS: • neutering • food intake • body weight • leptin • insulin • cats
EXPANDED ABSTRACT
Studies have shown that 25–40% of cats that visit veterinary hospitals are overweight or obese (1,2). The common practice of neutering the domestic cat is associated with an increased incidence of obesity (2,3) and it has been shown that both male and female cats significantly increase body weight after neutering (4–6). Body weight is regulated through control of energy intake and energy expenditure. Although it has been demonstrated that food intake increases 3 mo after neutering (6), it is not clear whether an increase in food intake is the primary cause of body weight gain in neutered cats. In ovariectomized rats and Syrian hamsters, obesity can occur without an increase in food intake (7,8).
In obesity, there is an excessively large storage of triacylglyceride in adipocytes. The amount of triacylglyceride that is stored within an adipocyte is controlled by numerous hormonal and enzymatic factors. The hormones leptin and insulin are among these factors and are part of a long-term signaling mechanism that regulates body fat store. Neutering abruptly decreases the normal circulating concentrations of gonadal hormones and may directly or indirectly alter the regulation of body fat mass by affecting leptin and insulin signaling. Lipoprotein lipase (LPL) is an enzymatic factor believed to affect triacylglyceride stores by acting as a gatekeeper of flow of free fatty acids into adipocytes (9). In this role, increases in adipose LPL activity are suggested to expand body triaclyglyceride stores. An extrapolation of this function of LPL has been the suggestion that gonadectomy-induced weight gain results from lost gonadal steroid suppression of adipose LPL activity (10).
In this study the effects of neutering on food intake, insulin and leptin were determined in normal and LPL-deficient cats. The aim of the study was to investigate the mechanism underlying the weight gain associated with neutering.
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MATERIALS AND METHODS |
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 TOP MATERIALS AND METHODS RESULTSDISCUSSIONLITERATURE CITED |
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13% fat), and water were available ad libitum except during an overnight food withholding period before D2O administration. The diet was nutritionally complete and balanced for all life stages of cats as determined by animal-feeding tests using Association of American Feed Control Officials (AAFCO) procedures. All animal husbandry and treatment was approved by the UC Davis Animal Care and Administrative Advisory Committee and the animals were maintained in accordance with the Guide for the Care and Use of Laboratory Animals (12). The cats were given the expanded diet for 2 mo before initiation of treatments. The normal and LPL-deficient cats were divided into two groups that were balanced for age, body weight and/or body fat mass and were randomly assigned to control and neuter treatments. Before neutering, all cats were food deprived overnight. One group of eight normal and one group of eight LPL-deficient cats were neutered by the standard open technique. Each neutered cat was anesthetized intravenously with ketamine (10.0 mg/kg) and diazepam (0.5 mg/kg) after being given 0.04 mg/kg atropine IM. The remaining normal and LPL-deficient intact cats served as control groups. Body weights were recorded weekly and average daily food intake was determined for all cats 7 d before and 14 d following neutering.
Body lean and fat masses were determined using the D2O isotope dilution method immediately before neutering (wk -1) and during wk 36. Food and water were withheld overnight before D2O administration. The D2O was administered in normal saline and injected intravenously at a dosage of 0.4 g/kg body weight. Jugular blood samples (3 mL) were taken for D2O enrichment analysis immediately before and 60 min after D2O injection. The deuterium enrichments in atom percent excess (APE) of the serum samples were determined by a Fourier transform infrared (FTIR) spectroscopy method (13). Total body water (TBW) was estimated from serum samples and the amount of lean body mass and fat body mass were calculated (14–16).
During wks -1, 5, 16 and 34, jugular blood (3 mL) was collected from all cats and immediately placed in EDTA containing tubes to prevent coagulation. Samples were centrifuged at 1200 x g for 10 min. Plasma was removed and frozen at -80°C until analysis. Plasma leptin and insulin concentrations were determined by radioimmunoassys (RIA) validated for cats (13,17).
The significant effects of neutering on body weight, weekly food intake, plasma insulin and leptin were determined by general linear model ANOVA (SAS Institute, Cary, NC). Effects of time and interaction of time, treatment and LPL genotype were evaluated in the ANOVA. The Pdiff procedure of SAS was used to determine whether differences were significant at P < 0.05 with an 
-critical Bonferroni adjustment for data analyzed by repeated measures. Body composition data were analyzed by one-way ANOVA for the effect of neutering using JMP (SAS Institute). Daily food intake data were analyzed for main effects resulting from treatment and time and the interaction of treatment and time by two-way ANOVA using JMP ANOVA (SAS Institute). Differences were considered significant at P < 0.05, unless otherwise stated, and an -critical Bonferroni adjustment was used for data analyzed by repeated measures.
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RESULTS |
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TOPMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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DISCUSSION |
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TOPMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The body weights of neutered cats were greater than those of intact cats by postneuter wk 3. Neutered cats continued to gain weight and then plateaued when body weight had increased by 28%. The weight gain observed in neutered cats was primarily the result of an increase in FBM (Table 1). Fat body mass of intact cats changed little over the 36-wk period. LPL-deficient cats gained body fat at a similar rate to that of normal cats, indicating that LPL is not required for deposition of fat in neutered cats. This observation is consistent with recently reviewed findings that appear to reduce the importance of LPL activity as a determinant of adipose triacylglyceride store (19).
Alterations in energy expenditure may further promote the weight gain observed in neutered cats. The effect of neutering on metabolic rate has been examined in cats with inconsistent results. In two separate studies involving the use of indirect calorimetry to estimate energy expenditure, it was shown that the resting metabolic rate of adult neutered cats (age at neutering, 18–24 mo) decreased but did not differ from that of intact cats (6), whereas the heat coefficients of neutered cats (age at neutering, 7 wk and 7 mo) were significantly lower than those of intact control cats (20).
Leptin and insulin were altered by neutering. In normal neutered cats, plasma leptin concentrations increased with FBM. Neutering appeared to have no effect on normal circulating leptin concentrations because intact cats with similar percentage body fat had similar leptin values (13). The increase in circulating leptin probably reflected increased production from an expanded fat mass rather than neutering. Although their body fat stores were similar, LPL-deficient cats had higher circulating leptin concentrations than those of normal cats. The cause for this observation was not apparent. Relative to normal cats, LPL-deficient cats may not be as sensitive to the negative feedback signal provided by leptin. However, this sensitivity may vary with diet and management conditions. Lipoprotein lipase deficient cats previously have been observed to be leaner than normal cats (15). An attractive explanation for this observation would be a greater than normal leptin production by existing adipose in LPL-deficient cats.
Plasma insulin concentrations increased before substantial changes in body weight in normal and LPL-deficient cats. The increase in plasma insulin concentrations may have been the result of the greater food intake observed in the neutered cats. The rise in insulin concentration was apparently ineffective in suppressing food intake.
In summary, the neutering of adult male cats causes an immediate increase in food intake. The rise in food intake is sufficiently large that it alone might drive the characteristically observed weight gain of neutering. Observations on circulating leptin and insulin concentrations indicate that the food-intake response is not suppressed by the negative feedback normally imposed by the hormones.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Supported by the George and Phyllis Miller Feline Health Fund, Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis.
4 Abbreviations used: D2O, deuterium oxide; FBM, fat body mass; HE, human equivalent; LBM, lean body mass; LPL, lipoprotein lipase; RIA, radioimmunoassay.
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LITERATURE CITED |
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TOPMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Scarlett, J. M. & Donoghue, S. (1998) Associations between body condition and disease in cats. J. Am. Vet. Med. Assoc. 212:1725-1731.[Medline]
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13. Backus, R. C., Havel, P. J., Gingerich, R. L. & Rogers, Q. R. (2000) Relationship between serum leptin immunoreactivity and body fat mass as estimated by use of a novel gas-phase Fourier transform infrared spectroscopy deuterium dilution method in cats. Am. J. Vet. Res. 61:796-801.[Medline]
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17. Hoenig, M. & Ferguson, D. C. (1989) Impairment of glucose tolerance in hyperthyroid cats. J. Endocrinol. 121:249-251.
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20. Root, M. V., Johnston, S. D. & Olson, P. N. (1996) Effect of prepuberal and postpuberal gonadectomy on heat production measured by indirect calorimetry in male and female domestic cats. Am. J. Vet. Res. 57:371-374.[Medline]
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