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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2148S-2150S, August 2004

Supplement: WALTHAM International Science Symposium: Nature, Nurture, and the Case for Nutrition

Rapid Weight Loss with a High-Protein Low-Energy Diet Allows the Recovery of Ideal Body Composition and Insulin Sensitivity in Obese Dogs1,2

Géraldine Blanchard*,3, Patrick Nguyen{dagger}, Constance Gayet{dagger}, Isabelle Leriche**, Brigitte Siliart{dagger} and Bernard-Marie Paragon*

* Nutrition Unit, National Veterinary School of Alfort, Maisons Alfort, France, {dagger} Nutrition and Endocrinology Unit, National Veterinary School of Nantes, Nantes, France, and ** Virbac France SA, Carros, France

3 To whom correspondence should be addressed. E-mail: gblanchard{at}vet-alfort.fr.

KEY WORDS: • dog • obese • weight loss • insulin • sensitivity • diet


EXPANDED ABSTRACT

Obesity and overweight are very common in dogs of all Western countries (1), increasing the risk of several different diseases such as cancers (2,3), osteoarticular disorders, or diabetes (4). Some studies of obesity in dogs also showed that insulin resistance (IR)4 is a prominent feature (5,6) that could result from changes in the somatotropic axis' activity. Receptors that bind insulin and insulin-like growth factor 1 (IGF-1) show immunological, structural (7), and functional analogies (8), which could explain that IGF-1 has an insulin-like activity, and participates in IR. Adipose tissue expresses tumor-necrosis factor alpha (TNF{alpha}), which could also be involved in IR. Indeed, an elevated expression of TNF{alpha} was documented in obese insulin-resistant rodents and humans (9). It is not clear that obesity induces such modifications of TNF{alpha} and IGF-1 in dogs. The aim of this study was to test the ability of a low-energy and high protein:energy–ratio diet to enable a rapid weight loss while preserving the lean body mass in dogs and to evaluate the influence of the obesity treatment on insulin sensitivity and two insulin resistance–related factors, TNF{alpha} and IGF-1.


   MATERIALS AND METHODS
TOP
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
Six adult obese male Beagle dogs aged 4–9 y old (5.5 ± 2.1 y), whose ideal body weight (iBW) and body composition had been previously determined were used. The dogs had developed a nutritional obesity one year previously as described elsewhere (10). Briefly, the dogs were fed ad libitum a high-energy diet (75% of the energy allowance from a dry diet, 4790 kcal metabolizable energy/kg (ME/kg) on dry matter basis, crude protein (CP) 71 g/Mcal ME, and 25% from a canned food, 3860 kcal ME/kg on dry matter basis, CP 91 g/Mcal ME). They were then given a commercial high-energy nutritionally balanced food (as fed 4420 kcal ME/kg; CP 71 g/Mcal ME) to maintain their high body weight. For this study, dogs whose BW exceeded iBW by at least 25% (141 ± 9%; 126–179%), were fed once daily a commercial diet, nutritionally balanced, and designed to treat obesity (in vivo 2520 kcal ME/kg as fed; 103 g CP/Mcal ME, thus approximately twice the minimum NRC 2004 minimum recommendation (11); L-carnitine 300 mg/kg)5.

The energy allowance (75 kcal ME/iBW0.67) corresponded to 50% of the maintenance energy requirements (MER) (12) using the dogs' target body weight (13); this design was chosen to induce a rapid weight loss (2–3%/wk) and to cover the minimal requirement in proteins as the protein:energy ratio of the diet was twice the minimum.

Body composition [fat (FM) and fat-free mass (FFM)] was determined, at ideal body weight (T1), during the obese state (T2), and after weight loss (T3), using dilution of a single dose of deuterium oxide (0.5 g/kg) (14).

The euglycemic hyperinsulinemic clamp technique (10) was performed at T1, T2, and T3 to assess the insulin sensitivity, for which changes were expressed as the relative change in the glucose infusion rates required to maintain euglycemia at either T2 or T3 compared to the glucose infusion rate at T1.

Plasma TNF{alpha} was measured using an enzymatic immunoassay, and plasma IGF-1 was performed with a commercial immunoradiometric assay as previously described (15). Both TNF{alpha} and IGF-1 were measured at T1, T2, and at wk 6, 9, 12, 15, 18, 21, and 23 during the weight-loss period.

Data were reported as mean ± SEM. Statistical analysis using the Instat Software package (Statview 5.0, Abacus Concept, Berkeley, CA) was performed with the two-sided Wilcoxon paired test to determine significant differences between parameters of normal and insulin-resistant dogs. IGF-1 and TNF{alpha} values were analyzed with an ANOVA (The SAS System 8.02 SAS Institute, Cary, NC). A P-value < 0.05 was considered statistically significant.


   RESULTS
TOP
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
After weight loss, the body weight of the dogs was similar to their ideal weight (Fig. 1). The duration of the weight-loss period was 42–161 d, with a mean of 85 ± 17 d, and a rate of –2.6 ± 0.4% of wt/wk.



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  		FIGURE 1  Dogs body weight (kg) when ideal (shaded bar), obese (solid bar), and after weight loss (open bar). Means ± SEM are indicated; n = 6. *P < 0.05; T2 differed from the other times based on Wilcoxon paired test.

 
The body fat-free mass after weight loss was similar to that assessed at ideal body weight (Fig. 2).



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  		FIGURE 2  Body composition of the dogs: fat mass as % of BW (%FM) and fat-free mass in kg (FFM), when ideal (%FM1 and FFM1), obese (%FM2 and FFM2), and after weight loss (%FM3 and FFM3). Means ± SEM are indicated; n = 6. *P < 0.05; T2 differed from the other times based on Wilcoxon paired test.

 
Insulin sensitivity was lower (P < 0.05) in obese dogs than in either of the other states, and did not significantly differ after weight loss from its initial value at ideal body weight (Table 1).


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  		TABLE 1 Insulin sensitivity as measured by the euglycemic hyperinsulinemic clamp method in 6 dogs at 3 body weights: ideal, obese, and after body weight reduction

 
TNF{alpha} and IGF-1 were higher in obese dogs than in either of the other states (Figs. 3 and 4). Plasma IGF-1 concentration was different across time (ANOVA, P = 0.0003). Plasma TNF{alpha} concentration was not, due to a high standard deviation (ANOVA, P = 0.19), but was significantly different among the three states: ideal, obese, and after weight loss (Wilcoxon paired test, P < 0.05).



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  		FIGURE 3  Insulin-like growth factor I (IGF-1) blood concentration in dogs when ideal (id, shaded bar), obese (ob, solid bar), and during weight loss (up to wk 23). Means ± SEM are indicated; n = 6. *P < 0.005; T2 differed from all other times based on ANOVA.

 


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  		FIGURE 4  Tumor necrosis factor alpha (TNF{alpha}) blood concentration in dogs when ideal (id, shaded bar), obese (ob, solid bar), and during weight loss (up to wk 23). Means ± SEM are indicated; n = 6. *ANOVA, P = 0.195; Wilcoxon paired test with ideal, obese, and after weight loss, P < 0.05.

 

   DISCUSSION
TOP
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
The results of this study showed that a restricted energy supply with a low-energy and high protein:energy–ratio diet allowed a very satisfactory weight loss in obese dogs, quantitatively and qualitatively, because dogs returned to their basal weight and fat-free mass. The higher fat-free mass absolute value in the obese state may have been related to higher body fluids in obese dogs. However, in the obese state the fat mass increased much more, and the percent of the fat-free mass diminished significantly, representing ~67% vs. 83% in the dogs with ideal body weight.

Human studies found that a high-protein diet did preserve lean tissue mass (16) and promoted the loss of fat tissue (17). A high-protein, energy-restricted diet was also successful in reducing the body weight and body fat of overweight dogs (18) and cats (19), and in conserving lean body mass of dogs (20). The conservation of fat-free mass during weight loss may also have been helped by the high L-carnitine content of the diet (300 mg/kg) as described previously in obese dogs, fed a diet of similar L-carnitine content (21).

TNF{alpha} and IGF-1 are considered to be blood markers of insulin resistance (9,22) because it was shown that their overproduction is linked to the pathogenesis of this syndrome. Indeed, TNF{alpha} is known to impair insulin receptor signaling (23). Hotamisligil et al. (9) provided evidence that TNF{alpha} levels increase in obese and IR rodents. Several studies (24,25) reported an increase in plasma TNF{alpha} level in obese insulin-resistant subjects. Many studies in the literature showed that elevated IGF-1 concentrations have an impact on insulin secretion, which could, over time, lead to IR (22,26). It was shown that plasma IGF-1 concentration was increased in insulin-resistant patients (27). This could have different effects. Because of its structural homology with insulin, IGF-1 can link to insulin receptors and then lead to a decrease in insulin clearance (28). Otherwise IGF-1 acts as a mitogenic factor and can stimulate ß-cell proliferation and then insulin secretion (29). It was shown that impairment in both TNF{alpha} and IGF-1 plasma concentration are associated with insulin resistance, in obese dogs, and this could explain, at least in part, the outbreak of this syndrome (15). Our results showed that the treatment of obesity could allow a return of these variables to normal levels, as previously demonstrated in humans (9). This showed that the changes in glucose metabolism observed in obese dogs suffering from a nutritional obesity are reversible, and the treatment of obesity is beneficial to the long-term health of these animals. Because it occurred rapidly in response to restriction of energy intake we can hypothesize that the return of TNF{alpha} and IGF-1 concentrations to normal values would have been the consequence of this restriction rather than decrease in adiposity.

In conclusion, this study showed that the high protein:energy–ratio, low-energy, high-fiber L-carnitine–enriched diet used here allowed a very rapid weight loss in obese dogs, without alteration in body composition compared to their ideal state. It also suggested that the treatment of obesity in dogs could be a factor in normalizing levels of insulin resistance.


   FOOTNOTES
 
1 Presented as part of the WALTHAM International Science Symposium: Nature, Nurture, and the Case for Nutrition held in Bangkok, Thailand, October 28–31, 2003. This symposium and the publication of the symposium proceedings were sponsored by the WALTHAM Centre for Pet Nutrition, a division of Mars, Inc. Symposium proceedings were published as a supplement to The Journal of Nutrition. Guest editors for this supplement were D'Ann Finley, James G. Morris, and Quinton R. Rogers, University of California, Davis. Back

2 Financial support was provided by Virbac S.A., Carros, France. Back

4 Abbreviations used: BW, body weight; CF, crude fiber; CP, crude protein; DM, dry matter; EE, ether extract; FFM, fat-free mass; FM, fat mass; GIR, glucose infusion rate; iBW, ideal body weight; IGF-1, insulin-like growth factor I; IR, insulin resistance; ME, metabolizable energy; TNF{alpha}, tumor necrosis factor alpha. Back

5 Virbac Vet Complex Chien Adult HypocaloriqueND, Laboratoire VIRBAC France SA, BP 447, F-06 515, Carros, France. Composition as fed: crude protein 26%; ether extract 8%; ash 7%; crude fiber 14%; DM 92%; calcium 1.2%; phosphorus 0.9% ; vitamin A 14,500 IU/kg; vitamin D-3 1450 IU/kg; vitamin E 145 mg/kg; copper 26 mg/kg (as copper sulfate); L-carnitine 300 mg/kg; 2520 kcal ME/kg (in vivo); 103 g CP/Mcal ME. Ingredients: bean pods, dehydrated animal proteins, cooked maize, deoiled soya, wheat bran, animal fats, beet pulp, linseed, maize gluten, vegetable fibers, sea salt, fructo-oligosaccharides, vitamins, minerals and trace elements, L-carnitine, chondroitin sulfate. NRC, National Research Council. Back


   LITERATURE CITED
TOP
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 

1. Edney, A. T. & Smith, P. M. (1986) Study of obesity in dogs visiting veterinary practices in the United Kingdom. Vet. Rec. 118: 391–396.[Abstract]

2. Glickman, L. T., Schofer, F. S., McKee, L. J., Reif, J. S. & Goldschmidt, M. H. (1989) Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J. Toxicol. Environ. Health 28: 407–414.[Medline]

3. Sonnenschein, E. G., Glickman, L. T., Goldschmidt, M. H. & McKee, L. J. (1991) Body conformation, diet, and risk of breast cancer in pet dogs: a case-control study. Am. J. Epidemiol. 133: 694–703.[Abstract/Free Full Text]

4. Mattheeuws, D., Rottiers, R., Kaneko, J. J. & Vermeulen, A. (1984) Diabetes mellitus in dogs: relationship of obesity to glucose tolerance and insulin response. Am. J. Vet. Res. 45: 98–103.[Medline]

5. Rocchini, A. P., Marker, P. & Cervenka, T. (1997) Time course of insulin resistance associated with feeding dogs a high-fat diet. Am. J. Physiol. 272: E147–E154.

6. Verwaerde, P., Galinier, M., Fourcade, J., Massabuau, P., Galitzky, J., Senard, J.-M., Tran, M.-A., Berlan, M. & Montastruc, J.-L. (1997) Anomalies du système nerveux autonome à la phase initiale du syndrome d'insulino-résistance: apport de l'étude de la variabilité de la fréquence cardiaque et de la pression artérielle sur un modèle d'obésité nutritionnelle. [Autonomic nervous system abnormalities in the initial phase of insulin resistance syndrome. Value of the study of variability of cardiac rate and blood pressure on a model of nutritional obesity.] Arch. Mal. Coeur Vaiss. 90: 1151–1154.[Medline]

7. Baxter, R. C., Martin, J. L. & Wood, M. H. (1987) Two immunoreactive binding proteins for insulin-like growth factors in human amniotic fluid: relationships to fetal maturity. J. Clin. Endocrinol. Metab 65: 423–431.[Abstract/Free Full Text]

8. Ullrich, A., Gray, A., Tam, A. W., Yang-Feng, T., Tsubokawa, M., Collins, C., Henzel, W., Le Bon, T., Kathuria, S., Chen, E., Jacobs, S., Francke, U., Ramachandran, J. & Fujita-Yamaguchi, Y. (1986) Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 5: 2503–2512.[Medline]

9. Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L. & Spiegelman, B. M. (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Invest. 95: 2409–2415.

10. Bailhache, E., Ouguerram, K., Gayet, C., Krempf, M., Siliart, B., Magot, T. & Nguyen, P. (2003) An insulin-resistant hypertriglyceridemic normotensive obese dog model: assessment of insulin resistance by euglycemic hyperinsulinemic clamp in combination with stable isotope technique. J. Anim. Physiol. Anim. Nutr. (Berl). 87: 86–95.[Medline]

11. National Research Council. (2004) Nutrient Requirements of Dogs and Cats. National Academic Press, Washington, DC.

12. Kronfeld, D. S. (1991) Protein and energy estimates for hospitalized dogs and cats. Purina International Nutrition Symposium, Orlando, FL. 5–11.

13. Laflamme, D. P., Kuhlman, G. & Lawler, D. F. (1997) Evaluation of weight loss protocols for dogs. J. Am. Anim. Hosp. Assoc. 33: 253–259.[Abstract]

14. Ferrier, L., Robert, P., Dumon, H., Martin, L. & Nguyen, P. (2002) Evaluation of body composition in dogs by isotopic dilution using a low-cost technique, Fourier-transform infrared spectroscopy. J. Nutr. 132: 1725S–1727S.[Abstract/Free Full Text]

15. Gayet, C., Bailhache, E., Dumon, H., Martin, L., Siliart, S., P. Nguyen, P. (2004) Insulin resistance and changes in plasma concentration of TNF{alpha}, IGF1, and NEFA in dogs. J. Anim. Physiol. Anim. Nutr. 88: 157–165[Medline]

16. Farnsworth, E., Luscombe, N. D., Noakes, M., Wittert, G., Argyiou, E. & Clifton, P. M. (2003) Effect of a high-protein, energy-restricted diet on body composition, glycemic control, and lipid concentrations in overweight and obese hyperinsulinemic men and women. Am. J. Clin. Nutr. 78: 31–39.[Abstract/Free Full Text]

17. Parker, B., Noakes, M., Luscombe, N. & Clifton, P. (2002) Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care 25: 425–430.[Abstract/Free Full Text]

18. Diez, M., Nguyen, P., Jeusette, I., Devois, C., Istasse, L. & Biourge, V. (2002) Weight loss in obese dogs: evaluation of a high-protein, low-carbohydrate diet. J. Nutr. 132: 1685S–1687S.[Abstract/Free Full Text]

19. Nguyen, P., Dumon, H., Martin, L., Siliart, B., Ferrier, L., Humbert, B., Diez, M., Breul, S. & Biourge, V. (2002) Weight loss does not influence energy expenditure nor leucine metabolism in obese cats. J. Nutr. 132: 1649S–1651S.[Abstract/Free Full Text]

20. Hannah, S. (1999) Role of dietary protein in weight management. Comp. Cont. Educ. Pract. Vet. 21: 32–33.

21. Allen, T. A. (1998) The effect of L-carnitine supplementation on body composition in dogs prone to obesity. In: L-carnitine What Difference It Makes? Proceedings of the Symposium Hill's Pet Nutrition, Leuven, Belgium. 35.

22. Leahy, J. L. & Vandekerkhove, K. M. (1990) Insulin-like growth factor-I at physiological concentrations is a potent inhibitor of insulin secretion. Endocrinology 126: 1593–1598.[Abstract/Free Full Text]

23. Uysal, K. T., Wiesbrock, S. M., Marino, M. M. & Hotamisligil, G. S. (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389: 610–614.[Medline]

24. Winkler, G., Lakatos, P., Salamon, F., Nagy, Z., Speer, G., Kovacs, M., Harmos, G., Dworak, O. & Cseh, K. (1999) Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet. Med. 16: 207–211.[Medline]

25. Zinman, B., Hanley, A. J., Harris, S. B., Kwan, J. & Fantus, I. G. (1999) Circulating tumor necrosis factor-alpha concentrations in a native Canadian population with high rates of type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 84: 272–278.[Abstract/Free Full Text]

26. Guler, H. P., Schmid, C., Zapf, J. & Froesch, E. R. (1990) Effects of insulin-like growth factor I in man. Acta Paediatr. Scand. Suppl. 367: 52–54.[Medline]

27. Loche, S., Cappa, M., Borrelli, P., Faedda, A., Crino, A., Cella, S. G., Corda, R., Muller, E. E. & Pintor, C. (1987) Reduced growth hormone response to growth hormone-releasing hormone in children with simple obesity: evidence for somatomedin-C mediated inhibition. Clin. Endocrinol. (Oxf.) 27: 145–153.[Medline]

28. Ullrich, A., Gray, A., Tam, A. W., Yang-Feng, T., Tsubokawa, M., Collins, C., Henzel, W., Le Bon, T., Kathuria, S., Chen, E., et al. (1986) Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 5: 2503–2512.

29. Smith, F. E., Rosen, K. M., Villa-Komaroff, L., Weir, G. C. & Bonner-Weir, S. (1991) Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas. Proc. Natl. Acad. Sci. USA 88: 6152–6156.[Abstract/Free Full Text]




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