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Nutrient Metabolism

Weight Gain in Gonadectomized Normal and Lipoprotein Lipase–Deficient Male Domestic Cats Results from Increased Food Intake and Not Decreased Energy Expenditure,

Department of Molecular Biosciences and ^* Department of Animal Science, University of California, Davis, CA 95616

³To whom correspondence should be addressed. E-mail: rcbackus{at}ucdavis.edu.

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Gonadectomy predisposes domestic cats to undesired body weight gain and obesity. The disturbance responsible for this disregulation of energy balance has not been clearly identified. Energy intake and expenditure, body composition and plasma concentrations of leptin, insulin, glucose and triacylglycerol were determined during a 36-wk period in adult male (2–5 y) gonadectomized (n = 8) and intact (n = 8) normal cats and gonadectomized (n = 8) and intact (n = 8) lipoprotein lipase (LPL)–deficient cats. Cats were housed individually in temperature- and light-controlled rooms and continuously provided a commercial dry-type diet. In normal and LPL-deficient cats, body weight increased (P < 0.05) after gonadectomy by 27 to 29%, mostly as a result of fat accretion. There was a rapid increase (P < 0.05) in food intake of 12% after gonadectomy of normal and LPL-deficient cats. The metabolic rate (kJ·kg^-1·d^-1), determined in normal intact (319 ± 20, n = 5) and gonadectomized (332 ± 36, n = 5) cats, did not differ after gonadectomy. After gonadectomy, plasma concentrations of glucose and triacylglycerol did not change, whereas plasma insulin and leptin concentrations increased (P < 0.05), but not coincidentally with body weight gain. A stair-step increase in energy intake, and not decreased energy expenditure, appears to drive the weight gain associated with gonadectomy. Body fat mass appears to increase until the energy intake supports no further expansion. Adiposity signaling through insulin or leptin does not appear to mediate the energy intake effect. LPL deficiency did not preclude development of the overweight body condition. Therefore, gonadectomy-induced weight gain in cats is not a result of changed adipose LPL activity, as previously suggested.

KEY WORDS: • food intake • insulin • leptin • metabolic rate • neutering

Epidemiological studies show that between 25 and 40% of domestic cats presented to veterinary practices are overweight or obese (1,2). These cats have an increased risk for developing lower urinary tract disease (3), diabetes mellitus, hepatic lipidosis (2), lamenesses and dermatoses (1). A factor that contributes to weight gain in cats is gonadectomy (4), a procedure widely used to control pet populations and reduce the incidence of undesired sex-specific behaviors.

The food intake of cats increases several weeks after gonadectomy (5). Although gonadectomy induces substantial weight gain, it is not clear whether this gain is the result of increased food intake or the increased food intake reflects energy demands of a greater body mass. In rats and hamsters, weight gain may occur without substantial change in food intake (6–9). Such weight gain results from reduced energy expenditure, and excess energy is stored in body fat. Observations of reduced fighting and roaming behaviors in male cats after gonadectomy are supportive of decreased energy expenditure as a cause for postgonadectomy weight gain (10). However, indirect calorimetry and energy balance findings (5,11–13) are not consistent in indicating that metabolic rate decreases after gonadectomy.

In our study, the food intake and metabolic rate of male domestic cats were determined soon after gonadectomy, before substantive change in body weight had occurred. The purpose was to identify whether the weight gain after gonadectomy was a result of increased energy intake or decreased energy expenditure. We determined plasma concentrations of insulin and leptin and measured energy intake and expenditure. We hypothesized that a gonadectomy-induced decrease in either circulating leptin or insulin may affect a decreased expenditure and increased intake of energy. The effects of gonadectomy were determined in normal cats and in cats with a heritable deficiency of lipoprotein lipase (LPL) activity (14). Wade and Gray (15) hypothesized that the weight gain of gonadectomy results from a loss of gonadal steroid suppression of adipose LPL activity. Implicit in their hypothesis is the assumption that the activity of LPL in adipose determines the extent of the body fat store, an idea advanced by Greenwood (16) in the "gatekeeper" hypothesis. In studying the effect of gonadectomy on LPL-deficient cats, we tested the gatekeeper hypothesis to gain insight into the nature of the underlying weight gain in domestic cats after gonadectomy.

	MATERIALS AND METHODS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Animals.

Sixteen normal male domestic cats (2 y) and 16 LPL-deficient male cats (2–5 y) were obtained from and studied at the Feline Nutrition and Pet Care Center, University of California, Davis. The LPL-deficient cats were originally derived from cats identified by Jones et al. (17) as being devoid of LPL enzymatic activity. The loss of LPL activity was previously determined to be the consequence of a single base-pair transition that results in a missense encoding of an LPL exon (14). All cats were housed in individual cages and water was made freely available. The normal cats and LPL-deficient cats were housed in rooms of separate facilities. Room light and dark periods were 14 and 10 h, respectively, and temperatures ranged from 17 to 26°C. The long duration of the experiment necessitated use of three batches of the commercial diet. For any given period during the experiment, all cats received the diet from the same batch. Husbandry and use of cats in the experiment were approved by the University of California, Davis, Animal Care and Use Administrative Advisory Committee. The cats were maintained in accordance with the Guide for the Care and Use of Laboratory Animals (18).

Diet.

The cats were presented with a commercial expanded dry-type diet (Purina ONE Salmon and Tuna Flavor; Ralston Purina, St. Louis, MO) for ad libitum consumption except during periods when the experiment protocol required withholding of the diet. As determined by the manufacturer, the diet’s "as is" composition was 34% crude protein, 12.5% crude fat, 1.0% crude fiber, 6.4% ash, 36.1% nitrogen-free extract and 9.9% moisture. Ingredients of the diet in decreasing order of proportion of diet weight were poultry by-product meal, ground yellow corn, brewers rice, soybean meal, corn gluten meal, salmon, tuna, beef tallow preserved with mixed-tocopherols, brewers dried yeast, phosphoric acid, calcium carbonate, animal digest, salt, potassium chloride, tetra sodium pyrophosphate, choline chloride, dicalcium phosphate, taurine, L-lysine monohydrochloride, vitamins E, A, B-12 and cholecalciferol, zinc sulfate, ferrous sulfate, L-alanine, riboflavin supplement, niacin, calcium pantothenate, manganese sulfate, biotin, thiamin monohydrate, folic acid, copper sulfate, pyridoxine (PN) hydrochloride, citric acid, menadione sodium bisulfate complex, calcium iodate and sodium selenite.

Body composition.

Lean body mass (LBM) and fat body mass (FBM) were determined by use of an isotopic dilution method (19). Determinations were conducted during the week before gonadectomy (wk -1) and during wk 36 after gonadectomy. For this measurement, food and water were withheld overnight before and during the period of isotopic equilibration. Hypertonic saline (223 g/L sodium chloride) was added to deuterium oxide (D₂O; Cambridge Isotope Laboratories, Andover, MA) to produce an isotonic solution (9 g/L sodium chloride). The solution was injected intravenously (IV) so that cats received 0.4 g D₂O/kg body. Jugular blood samples (3 mL) were collected immediately before and at 60 min after the injections. Enrichment of D₂O in serum, total body water, LBM and FBM were determined as previously described (20).

Biochemical determinations.

Serum leptin concentrations were determined with a commercial RIA kit (Multi-species Leptin RIA Kit; Linco Research, St. Louis, MO). The kit was previously validated for use on cat serum (20). The lipemic serum of LPL-deficient cats interfered with pellet formation needed in the RIA. Lipid from samples was removed before assays to facilitate pellet formation. For this, 150 µL of sample serum was centrifuged at 16,000 x g for 10 min and 100 µL of the lipid-depleted infranate was assayed for leptin concentration. Validity of use of the lipid extraction was supported by the finding of parallelism of infranate dilutions with standard dilutions.

Plasma insulin concentrations were determined by an RIA validated for use in cats (21). Assays were conducted by the laboratory of Margarethe Hoenig, University of Georgia, College of Veterinary Medicine, Department of Physiology and Pharmacology, Athens, GA.

Plasma glucose and serum triacylglycerols were measured by use of colorimetric assay kits (Kits 510 and 339, respectively; Sigma). Samples from LPL-deficient cats were depleted of lipid as described in the leptin assay procedures.

Energy expenditure.

Energy expenditure was determined by a modification of the double-label water method used in cats, as described by Ballevre et al. (22). After withholding of food and water overnight, cats were given by IV injection 0.7 g/kg of D₂O and 0.13 g/kg of oxygen-18 water (Isotec, Miamisburg, OH). The isotopic water was salinized as described for injected D₂O solutions. Dilution spaces and fractional rate of washout of the water labels were determined from enrichments of the labels in serum collected immediately before injection, at the time of equilibration (1 h postinjection), and during d 2, 5, 7 and 12 after injection. Serum samples were obtained from 2 mL jugular venous blood. Enrichments of D₂O were determined by gas-phase Fourier transform infrared spectrometry (20), and those of oxygen-18 water were determined by isotope ratio mass spectrometry (Mountain Mass Spectrometry, Evergreen, CO). The rate of carbon dioxide production was determined by use of the D₂O and oxygen-18 kinetic data in the two-pool model. Energy expenditure was estimated from the carbon dioxide production and the respiratory quotient expected in oxidation of the diet, a "food quotient." The food quotient was calculated from the expected carbon dioxide production and oxygen consumption resulting from oxidation of dietary protein, fat and carbohydrate (23). A food quotient value of 0.85 was calculated for the commercial diet used.

On the day during which water isotopic labels were injected, LBM and FBM were determined from the body weight determined on that day and the total body water mass indicated by the oxygen-18 water dilution space. The assumptions used in the calculations are the same as those described for the determination of body composition using D₂O dilution.

Energy intake.

Food intake was determined from the weight of diet consumed. Because of the low moisture content of the diet (10% "as is" weight), daily variations in diet weight that might have been contributed by varying the moisture content were not considered substantial, and therefore were not considered in food intake determinations. Energy intake was determined as food intake times diet energy density (16 kJ/g, according to the diet manufacturer). To normalize for metabolic mass differences, energy intake was expressed on the basis per LBM to the power.

Experimental design.

Before experimental procedures were begun, all cats had been presented with the dry-expanded diet for 22 wk, and their body weights were stable. Normal cats were assigned to two groups balanced for number, age and body weight. LPL-deficient cats were assigned to two groups by use of the same criteria. After group assignments, energy expenditure determinations were begun in 5 cats from each of the normal cat groups. LBM and FBM of these cats (n = 10) and those of the remaining normal (n = 6) and LPL-deficient (n = 16) cats were determined from isotopic dilution and body weight measurements. Approximately 3 wk later, one group of the normal cats and one group of the LPL-deficient cats were gonadectomized by the standard open technique (24). For this, the cats were premedicated with atropine (0.04 mg/kg, intramuscularly) and anesthetized with ketamine and diazapam (10.0 and 0.5 mg/kg, IV, respectively). Intact normal and LPL-deficient cats served as control animals. So that preoperative food restriction would not obscure observations on the effects of gonadectomy, food was withheld overnight from the control cats as well as from the cats to be gonadectomized.

Of the 10 normal cats in which energy expenditure was determined, 5 cats were gonadectomized and 5 cats remained intact. Energy expenditures and body composition were again determined in these cats 17 d after gonadectomy. Body composition was determined from deuterium dilution and body weight measurements in all cats during the last week of the experiment, wk 36.

During the week preceding gonadectomy, jugular venous blood (3 mL) was collected from each cat. The blood sampling was repeated in each cat during postgonadectomy wk 2, 5, 8, 12, 16 and 34. Leptin, insulin, glucose and triacylglycerol concentrations in plasma of the samples were determined.

Statistics.

Effects of gonadectomy on body weight, food intake, serum triacylglycerols, plasma insulin, leptin and glucose were determined by general linear model (GLM) ANOVA (SAS Institute, Cary, NC). Effects of time and interaction of time, treatment and LPL genotype were evaluated in the ANOVA. Differences between treatments were determined by single degree of freedom contrasts within the ANOVA. Daily food intake observations were analyzed for main effects attributed to treatment and time and the interaction of treatment and time by two-way ANOVA. Through use of the Proc GLM and ANOVA, differences were considered significant at P < 0.05, with critical Bonferroni adjustment for data analyzed by repeated measures. A main effect was considered a trend when 0.05 < P 0.10. Differences in body composition and energy expenditure of gonadectomized and intact cats were analyzed by use of paired and two-sample Student’s t tests.

	RESULTS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Food intake.

For 2 wk preceding gonadectomy, the food intakes of cats to be gonadectomized did not differ (P > 0.05) from those of cats that were left intact (Table 1). Food intake of both intact and gonadectomized cats substantially increased after the day of gonadectomy (Fig. 1), which was probably a compensatory response to the withholding of food from all cats during the perioperative period. For gonadectomized cats, food intakes did not decline to the pregonadectomy levels in the intact cats. One normal gonadectomized cat consumed only 7 g of diet the day after gonadectomy, whereas other normal gonadectomized cats consumed 105 g of diet on that day. The low food intake of this cat was attributed to a prolonged postoperative recovery, and the food intake for the cat during postoperative wk 1 was excluded from statistical analyses.

View larger version (31K): [in this window] [in a new window]   FIGURE 1 Mean daily food intake of normal intact and gonadectomized (GX) cats (upper plot) and LPL-deficient intact and GX cats (lower plot) 20 d before and 28 d after gonadectomy date (marked by arrow in upper plot). Open boxes indicate 12-d periods of isotopic washout used in double-label water determinations of energy expenditure. Errors bars represent SEM, n = 8. *Different from intact cats, P < 0.05.

Body weight.

Body weights of cats that were gonadectomized increased and remained elevated for the duration of the experiment (Fig. 2). By wk 7 postgonadectomy, body weights of gonadectomized normal cats and gonadectomized LPL-deficient cats had increased so that their body weights were greater (P < 0.05) than those of the intact normal and LPL-deficient cats. The rate of increase in body weight among the gonadectomized cats slowed with time, with plateaus in body weight. There were maximal body weights at postgonadectomized wk 30 and 32 for the normal and LPL-deficient cats, respectively. These body weights were 29 to 31% greater than body weights of the intact cats during the same week after gonadectomy. Body weights of intact cats did not change (P > 0.05) during the experiment.

View larger version (28K): [in this window] [in a new window]   FIGURE 2 Mean body weights of normal intact, normal gonadectomized (GX), LPL-deficient intact and LPL-deficient GX adult male cats before and after gonadectomy. Errors bars represent SEM, n = 8. *Different from intact cats, P < 0.05.

Before gonadectomy, the FBM and LBM of normal and LPL-deficient cats selected to be gonadectomized did not differ (P > 0.05) from those of cats selected to be left intact (Table 2). At wk 36 postgonadectomy, the FBM of gonadectomized normal and gonadectomized LPL-deficient cats was greater (P < 0.01) than the FBM of the respective intact groups of cats, increasing by 109 and 108%, respectively.

Before gonadectomy, the body weight, isotopic dilution spaces and elimination rate constants, and FBM and LBM of cats to be gonadectomized (n = 5) did not differ (P > 0.05) from those of cats to be left intact (n = 5) (Table 3). Between the beginning and the end of the first and second isotopic washout periods, body weights of the intact cats did not differ (P = 0.51). Body weights of the gonadectomized cats (n = 5) were 6% greater than their pregonadectomized body weights, although the increase was not significant (P = 0.06). FBM and LBM of the gonadectomized and intact cats also did not differ (P > 0.6) between the washout periods.

View larger version (27K): [in this window] [in a new window]   FIGURE 3 Mean daily energy expenditures of adult male cats left intact (n = 5) or gonadectomized (n = 5) expressed on a per animal, per unit body weight and per unit metabolic lean body mass basis. Energy expenditures were determined by the double-labeled water method over two 12-d periods, the first period beginning 20 d before gonadectomy (Pre-) and the second period beginning 17 d after gonadectomy (Post-). Errors bars represent SEM.

View larger version (38K): [in this window] [in a new window]   FIGURE 4 Mean daily metabolizable energy intakes normalized for metabolic lean body mass (kg3/4) of adult male cats left intact (n = 5, Group 1) or gonadectomized (GX) (n = 5, Group 2). Energy intakes were determined over two 12-d periods, the first period beginning 20 d before gonadectomies and the second period beginning 17 d after gonadectomies. Errors bars represent SEM. *Indicated means differ, P < 0.01.

Among both normal and LPL-deficient cats, plasma insulin concentrations of cats selected to be gonadectomized did not differ (P > 0.05) from cats selected to remain intact. For normal cats, plasma insulin concentrations of gonadectomized cats did not differ (P > 0.05) from those of intact cats at wk 2 (Table 4). At wk 5, 8, 12 and 16, plasma insulin concentrations of the normal gonadectomized cats were greater (P < 0.05) than those of the normal intact cats. For LPL-deficient cats, plasma insulin concentrations of gonadectomized cats were greater (P < 0.05) than those of intact cats at all times that samples were obtained (wk 2, 5, 8, 12 and 16) (Table 5). Plasma insulin concentrations after gonadectomy of normal gonadectomized cats and those of gonadectomized LPL-deficient cats were 243 ± 18 and 303 ± 42 pmol/L, respectively. Over the same period, plasma insulin concentrations of normal intact cats and those of intact LPL-deficient cats were 165 ± 14 and 178 ± 8 pmol/L, respectively.

Among normal cats, plasma leptin concentrations of cats selected to be gonadectomized did not differ (P > 0.05) from those of cats selected to be left intact (Table 4). Among LPL-deficient cats, there was an unexplainable difference (P < 0.05) in plasma leptin concentrations in cats selected to be gonadectomized and those of cats selected to remain intact (Table 5). Initial FBM were not different between the two groups of LPL-deficient cats (Table 2, wk -1). After gonadectomy of normal and LPL-deficient cats, plasma leptin concentrations increased, but not until late in the trial. During wk 34, plasma leptin concentrations of gonadectomized normal (2.9 ± 0.4 µg/L) and gonadectomized LPL-deficient cats (6.0 ± 1.4 µg/L) were greater (P < 0.05) than those of the respective control cats, intact normal (1.8 ± 0.2 µg/L) and intact LPL-deficient cats (2.7 ± 0.3 µg/L). In both normal and LPL-deficient cats, plasma leptin concentrations in gonadectomized cats did not differ (P > 0.05) from those of intact cats during wk 2, 5, 8, 12 and 16. However, in LPL-deficient cats, there was a trend of greater plasma leptin concentrations in gonadectomized cats than in intact cats at postgonadectomized wk 5 (P = 0.07) and 16 (P = 0.08). Across all weeks, plasma leptin concentrations of normal cats (1.7 ± 0.1 µg/L, pooled least-squares mean ± SEM) were less (P < 0.01) than those in LPL-deficient cats (2.4 ± 0.1 µg/L).

Glucose and triacylglycerol.

Plasma glucose concentrations of gonadectomized normal cats did not differ (P > 0.05) from plasma glucose concentrations in intact cats either before or after gonadectomy (Table 4); there was a similar observation in LPL-deficient cats (Table 5). Plasma glucose concentrations of normal cats (5.2 ± 0.1 mmol/L, pooled least-squares mean ± SEM) were 13% less (P < 0.01) than those in LPL-deficient cats (5.9 ± 0.1 mmol/L).

Plasma triacylglycerol concentrations in gonadectomized normal cats did not differ (P > 0.05) from serum triacylglycerol concentrations in intact normal cats either before or after gonadectomy (Table 4). At every sampling time, serum triacylglycerol concentrations of LPL-deficient cats (247 ± 19 mmol/L, pooled least-squares mean ± SEM) were greater (P < 0.01) than those of normal cats (26 ± 2 mmol/L). Although serum triacylglycerol concentrations of LPL-deficient cats were substantially greater than those of normal cats, pre- and postgonadectomized serum triacylglycerol concentrations did not differ (P > 0.05) between LPL-deficient cats that were gonadectomized and those that were intact (Table 5).

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Gonadectomized normal cats weighed significantly more than intact normal cats by postgonadectomy wk 7. Although the body weight of the intact cats did not differ thereafter, the body weight of the gonadectomized cats increased to plateau weights 28% greater than those before gonadectomy (Fig. 2). The extent of the body weight increase was consistent with previous reports on the effect of gonadectomy (4,5,12,13,25–27). As indicated by body composition determinations, the increase in body weight was primarily a result of a doubling in the amount of body fat (Table 2). LBM increased by 10%, an increase probably resulting from changes required to support the expanded fat mass.

Decreases in metabolic rate of >25% were reported in cats after orchectomy and ovariohysterectomy (2,5,12). These reports have prompted the suggestion that reduction in energy expenditure contributes to the gain in body weight after the procedures. In the present experiment, energy expenditure did not differ after gonadectomy (Table 3, Fig. 3). The apparent inconsistency of findings might be explained in how energy expenditure is expressed. In previous indirect calorimetry studies, metabolic rates were determined well after postgonadectomy weight gains, and metabolic rates were expressed on a per body weight basis. Because fat mass is less metabolically active than lean mass (28), comparisons of metabolic rates between fat and lean individuals are difficult to interpret for the purpose of identifying the cause of weight gain. In the present study, the body weight gain after gonadectomy resulted mostly from increased fat mass. Therefore, a better comparison for identifying the cause of weight gain would be one based on lean mass energy expenditures. Martin and colleagues (13) made such a comparison, and their findings are consistent with those of the present study: energy expenditure on a lean mass basis of gonadectomized cats is not significantly (P > 0.14) different from that of intact cats.

A sex effect may confound interpretation of energy expenditure findings in cats. Fettman et al. (5) reported differences in metabolic rates between intact and ovariohysterectomized females greater than those between intact and orchectomized males. In their study of female cats, Flynn et al. (11) reported that food intake must be restricted by 24 to 30% to prevent weight gain after ovariohysterectomy. Using a similar paradigm, Hoenig and Ferguson (29) also reported that restriction in food intake is needed to prevent postovariohysterectomy gain in females. In contrast, these investigators reported that if gonadectomized male cats are given the same amount of food after gonadectomy as they receive before gonadectomy, there is no change in body weight.

Although it would appear that reduced energy expenditure might contribute to weight gain in ovariohysterectomized cats, Martin et al. (13) reported no effect of ovariohysterectomy on energy expenditure. These and the present investigators allowed cats free access to food. For food-restricted gonadectomized cats, it is possible that lean mass contracts, whereas fat mass expands. The possibility of contracted lean mass in weight balance studies could be confirmed through body composition determinations.

Unlike with energy expenditure, there is general agreement on the effect of gonadectomy on food intake. Gonadectomized cats consume more diet than intact cats when the food intake of the cats is determined several months after gonadectomy (5,12). The present work shows that increased food intake is an early event, occurring as early as d 2 after gonadectomy (Fig. 1). We ascertained that, through postgonadectomy wk 11, the increase in food intake is not transient but sustained (Table 1). This acute effect on food intake is probably a result of withdrawal of gonadal hormones. There is an abrupt decrease in circulating testosterone concentration after gonadectomy in other species (30–32), and such a reduction in gonadal hormone concentration is associated with changes in food intake in rats (33–36). Curiously, the effects of gonadectomy in our male cats are more similar to those reported in female than in male rats. Ovariectomy increases food intake and orchectomy decreases food intake in rats (37,38). The deviation of effect in male cats from that in male rats may be a species variation in dependence of food intake on estrogens. Estrogens in males are produced from gonadal androgens by activity of tissue aromatases (39). Although sources and amounts of estrogens in male and female cats may differ, food intake in both sexes may be modulated by estrogen, so that with gonadectomy, inhibition of food intake by estrogens may be lost in both sexes.

Current models of energy homeostasis divide regulation of energy balance into peripheral and central systems. Insulin and leptin are believed to be adiposity signals of the peripheral system that indicate status of body energy stores to the central system. Because secretion and potency of these hormones are modified by gonadal hormones (40,41), we postulated that gonadectomy might cause a decline in either plasma insulin or leptin concentrations, and effects of gonadectomy might then only reflect responses to a misperceived state of energy deficiency. However, after gonadectomy, plasma concentrations of insulin and leptin were initially unchanged (Table 4, wk 2 vs. wk -1) or increased (Table 5, wk 2 vs. wk -1) rather than decreased. Therefore, the increase in food intake induced by gonadectomy would appear to occur independent of change in signaling through insulin or leptin.

Given the reputed roles of insulin and leptin as adiposity signals, it is not clear why plasma concentrations of the hormones did not acutely parallel changes in body fat. Plasma insulin concentrations were presently determined in animals consuming diet ad libitum. Therefore, the greater plasma insulin concentrations in gonadectomized cats relative to those in intact cats may have mostly reflected insulin response to the greater food intakes of gonadectomized cats relative to those of intact cats. An increased insulin resistance in the gonadectomized cats would explain the difference in plasma insulin findings later, after substantial gain in fat mass. Other investigators reported that fasting insulin concentrations are positively correlated with body weight (and presumably body fat) and suggest the relationship is evidence of insulin resistance in cats (26,42).

Circulating leptin concentrations in cats are positively correlated with FBM (20,43). The greater leptin concentrations in gonadectomized cats relative to those in intact cats are consistent with this relationship, but only at postgonadectomy wk 36. Gonadectomy may delay or attenuate the leptin secretory response of adipocytes, which secrete leptin in proportion to their mass (44). If this is the case, a greater expansion of adipose mass in gonadectomized animals may be needed to produce an effective leptin feedback signal.

Lipoprotein lipase is produced in many tissues and its production is highly regulated. It has catalytic and ligand functions that make it an important element of body fat metabolism (45). The best evinced physiological roles of LPL are the clearing of lipoproteins from plasma and the provision of tissues with fatty acids bound in lipoprotein triacylglycerols. The importance of LPL catalytic activity is underscored by observations of a characteristic lipemia in LPL-deficient animals. Indeed, in LPL-deficient cats of the present study, serum triacylglycerol concentrations were 10 times greater than those of normal cats (Tables 4, 5).

Another characteristic of LPL-deficient animals is a lean (46) to normal body condition (47). To our knowledge, obese and overweight LPL-deficient animals have not been reported. The finding of a lean state in LPL-deficient cats would appear consistent with the physiological role of LPL. However, in our study, the body weight of gonadectomized LPL-deficient cats increased to a plateau (Fig. 2) that was 29% greater than the pregonadectomy weight (Table 2, weight at wk -1 vs. wk 36). The rate of increase in body weight paralleled that in the normal gonadectomized cats (Fig. 2, Table 2). These findings demonstrate that LPL activity is unnecessary for development of an overweight body condition and appear to contradict the suggestion that body weight gain induced by gonadectomy results from a loss of gonadal hormone suppression of adipose LPL activity (15). Therefore, although gonadal hormones affect LPL activity (48–50), gonadectomy-induced weight gain does not appear to be dependent on changed LPL activity in cats.

Our findings might indicate that supply of fatty acids from lipoproteins is not required for accretion of excessive body fat in cats. An alternate path for provision of fatty acids to adipose in LPL-deficiency might be through de novo synthesis of fatty acids (51), although evidence for such synthesis in substantive amounts is lacking (52). In LPL-deficient cats, lipases other than LPL [e.g., hepatic (53) or endothelial lipase (54)] may act on the extraordinarily high concentration of circulating lipoproteins in LPL-deficient animals to produce fatty acids in excess of adjacent tissue needs. These free fatty acids may be of sufficient abundance that FBM is expanded as a result of their storage in remote adipose depots.

In conclusion, our findings indicate that the weight gain characteristically associated with the gonadectomy of male domestic cats results principally from an expansion of fat mass driven by an increase in food intake. Reduction in metabolic rate does not appear to contribute to the weight gain as in other species. With gonadectomy, FBM probably expands until energy requirements to support the mass are just met by energy intake. The increase in food intake is rapid in onset and does not appear to be a response to loss of feedback inhibition by adiposity signaling through insulin or leptin. The rate and degree of increase in fat mass in gonadectomized LPL-deficient cats are similar to those in the gonadectomized normal cats. Therefore, the weight gain of gonadectomy is probably not the result of removal of gonadal hormone inhibition of adipose LPL activity. Because orchectomy and ovariohysterectomy are practically unavoidable in the management of domestic cats, a useful focus of future research on prevention of obesity in cats would be the study of mechanisms of control of food intake.

	ACKNOWLEDGMENTS

 
We thank the Raltson Purina Company for provision of diet, and Thomas R. Famula of the Department of Animal Science, University of California, Davis, for direction on statistical analyses.

	FOOTNOTES

 
¹ Supported by the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis.

² Presented at the Waltham International Symposium on Pet Nutrition and Health, Vancouver, BC, Canada August 6–8, 2001 [Kanchuk, M. L., Backus, R. C., Calvert, C. C., Morris J. G. & Rogers, Q. R. (2002) Neutering induces changes in food intake, body weight, plasma insulin and leptin concentrations in normal and lipoprotein lipase-deficient male cats. J. Nutr. 132: 1730S–1732S (abs.)] and at the Joint Nutrition Symposium, Antwerp, Belgium, August 21–25, 2002 [Backus, R. C., Kanchuk, M. L., Morris, J. G., Rogers, Q. R. (2002) Early effects of neutering on the energy intake and expenditure of domestic cats (Felis catus). Symp. Comp. Nutr. Soc. 4: 97 (abs.)].

⁴ Abbreviations used: FBM, fat body mass; LBM, lean body mass; LBM^3/4, metabolic lean body mass; LPL, lipoprotein lipase.

Manuscript received 30 November 2002. Initial review completed 29 December 2002. Revision accepted 20 February 2003.

	LITERATURE CITED

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

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