Excess weight is the most common medical condition in companion animals and has a number of health and wellness implications for both pets and their owners.
It is generally accepted that the prevalence of overweight and obese pets has increased in recent years. Excess weight is the most common medical condition in companion animals and has a number of health and wellness implications for both pets and their owners.
(Photo by Gregory Kindred)
Certain behaviors predispose dogs to weight gain. In Part 1 of this two-part series, we explore common causes of weight gain in dogs and the consequences of dogs being overweight or obese. In Part 2, we discuss treatment and monitoring strategies.
Obesity is defined as excessive white adipose tissue.1 Human epidemiologic data show increased morbidity and mortality with increasing body fat mass.2 The most commonly used measure of body fat in people is the body mass index (BMI: weight [kg] divided by height2 [m]). People are defined as
Individuals who are overweight or obese have an increased risk of cardiovascular disease and certain cancers and of overall mortality.7-10
Data from companion animals are more limited, and the definition of obesity is more arbitrary. Dogs are overweight when their weight is > 15% above ideal and are obese when their weight is > 30% of ideal.11,12 However, these criteria have not been confirmed with rigorous epidemiologic studies, and limited data exist on the definition of an optimal body weight. In most animals, obesity results from an imbalance between energy intake and energy expenditure.
Obesity is one of the most important medical problems in dogs. Studies from throughout the world have estimated the prevalence of overweight or obese dogs to range between 22% and 40%.13-17 Cross-sectional data suggest one in three dogs seen by U.S. veterinarians is overweight.18
Recent data in various animal species provide new insight into the genetic basis of obesity.19-21 A significant breed predisposition to obesity has been shown in certain breeds including Cairn terriers, West Highland white terriers, Scottish terriers, Shetland sheepdogs, basset hounds, Cavalier King Charles spaniels, dachshunds, beagles, cocker spaniels, and Labrador retrievers.12,15,22-24 Conversely, certain breeds, particularly sight hounds, appear to be resistant to the development of obesity.24
As an adult animal ages, lean body mass declines, resulting in a decrease in total daily energy needs.25 The loss of lean body mass is exacerbated if aging is accompanied by a decrease in voluntary activity. The total daily energy needs of an average-sized 7-year-old dog may decrease by as much as 20% when compared with its needs as a young adult. If food intake does not decrease proportionately with the decreasing energy needs, weight gain results.26 The end result is an increasing prevalence of obesity in older dogs. In short, a reduced metabolic rate associated with aging predisposes dogs to being overweight or obese.27
Neutering results in the net loss of circulating sex hormones, slowing an animal's metabolism and predisposing the neutered animal to becoming overweight or obese.14,15,28 Changes in sex hormones after neutering directly affect the satiety center in the brain through changes in leptin and ghrelin concentrations and possibly indirectly affect it by altering cell metabolism and hormonal regulators of food.24,29-31
Gonadectomy in dogs also results in modified feeding patterns. Compared with before surgery, four female ovariectomized beagles fed ad libitum for three months after surgery ate significantly more food and gained more weight.28 The study suggested that energy intake should be reduced by 30% after ovariectomy to maintain optimal body weight for a period of six months.28 These results confirmed those of a previous experiment that also used four young adult female beagles and showed that energy requirements are 20% lower after ovariectomy.31
Certain medications may also contribute to obesity in dogs. Phenobarbital, a common anticonvulsant, causes polyphagia at high serum concentrations. The increase in food consumption may contribute to a worsening body condition, resulting in an overweight or obese dog. Glucocorticoids stimulate gluconeogenesis and abdominal lipogenesis, which may contribute to fat deposition and weight gain.
Excessive white adipose tissue impacts canine health through two main mechanisms. First, excessive fat deposition may have physical effects on the body, including excessive weight bearing, which worsens orthopedic diseases; constriction of upper airways, which exacerbates respiratory disorders; an inability to groom, which leads to dermatologic issues; and an insulating effect, which causes reduced heat dissipation. Second, the normal endocrine function of white adipose tissue may be disturbed, a now-recognized significant pathogenetic mechanism for the development and exacerbation of many of the obesity-associated metabolic disorders in both humans and domestic animal species.32
White adipose tissue is an active endocrine organ, secreting protein modulators called adipokines (Table 1).33-37 Adipokines have proven endocrine, autocrine, and paracrine roles, regulating energy balance, immune function, angiogenesis, glucose and lipid metabolism, and hemostasis in people, dogs, and cats.34,38-40 Proinflammatory adipokines secreted by white adipose tissue increase as tissue mass rises. Thus, obesity may be viewed as a state of chronic inflammation. Increases in inflammatory adipokines have been causally linked to the development of metabolic syndrome and other obesity-related disorders in people.37,40 Increased inflammatory adipokine gene expression has also been documented in canine white adipose tissue.20
Table 1: Common Adipokines in Dogs*
Dietary factors also contribute to excessive weight gain in dogs. The number of meals and snacks fed, the consumption of table scraps, and an animal's presence when owners prepare or eat their own meals all contribute to canine weight gain.41 The cost of pet food has been shown to have a variable effect; a study showed that obese dogs were more likely to be fed a higher volume of cheaper brand foods than premium brands.42 Additionally, dogs with elderly owners were more likely to be overweight or obese, potentially because of poor dietary habits since the nutrition of the elderly owners was not ideal and, thus, supportive of obesity.15
Overweight or obese owners
In people, exposure to environments with a high prevalence of overweight and obese people leads to inaccurate perceptions of what constitutes a normal body shape.41 This misperception may also contribute to the increasing prevalence of obesity within the canine population.
A recent survey study collected data from 829 dog owners through personal interviews.43 Owners were asked to subjectively evaluate their dogs' body condition score (BCS). In addition, both the owner's BMI and the dog's BCS were assessed and recorded by the interviewer. Obese dogs were twice as likely to have obese owners as nonobese dogs were. Owner underestimation of a dog's BCS was nearly 20 times more common in dogs that were obese than in normal or underweight dogs. No significant relationship was found between owner underestimation of a dog's BCS and owner obesity. Interestingly, while obese owners are more likely to have obese dogs, they do not appear to differ in their misperception of their dogs' BCS when compared to nonobese owners.
Owner misperception of an obese dog's BCS presents a major obstacle in weight management. This misperception appears to be independent of whether the owner is obese. That is in contrast to the situation with obese children and parents, where obese parents consistently fail to recognize (or acknowledge) obesity in their children.44 Targeting this misperception of BCS with education is a requisite for successfully preventing and treating canine obesity.
A recent survey sought to identify environmental risk factors for canine obesity.45 In the study, 829 interviews were conducted (400 at a charity practice, 429 in private practice) in which owners were asked about their feeding and exercise habits, the household income, and their age. The BCSs of 696 dogs 1 year of age or older were assessed by using the seven-point S.H.A.P.E. (size, health, and physical evaluation) morphometric technique. Those dogs with a BCS 5/7 were considered mildly overweight, those with a BCS 6/7 were considered moderately overweight, and those with a BCS 7/7 were designated extremely overweight.
Using the seven-point scale, 35.3% (n=246) of the dogs were above their ideal body condition, 38.9% (n=271) were overweight, 20.4% (n=142) were obese, and 5.3% (n=37) were underweight.
Obese dogs had a higher median age and were more likely to be female and neutered. Obese dogs had significantly less exercise per week compared with nonobese dogs. Socioeconomic class appeared to be a factor in a dog's becoming overweight or obese; the risk of obesity was significantly associated with owner income as pet owners in the highest income bracket were more likely to have obese dogs. Finally, increasing owner age was also associated with increased incidence of overweight or obese dogs.45
It is generally well-known that obesity has many consequences in people. We are now beginning to recognize the many potential consequences obesity has in dogs, as well (Table 2).
Table 2: Potential Consequences of Overweight or Obesity in Dogs
As in people, obesity adversely impacts longevity in dogs. In one study in which 24 pairs of Labrador retrievers were randomly assigned to an ad libitum feeding group or an energy-restricted group (fed 75% of the amount consumed by the respective pair mate), the energy-restricted group's BCS was closer to the optimal score than the ad libitum feeding group's BCS was.46 The energy-restricted animals lived 1.8 years longer, had improved glucose tolerance (body fat mass and insulin resistance were correlated—the threshold range for increased insulin resistance was 5,000 g of body fat—energy-restricted dogs had lower body fat composition), and had reduced risk of orthopedic disorders such as osteoarthritis.
Diabetes mellitus and hypothyroidism are frequently associated with canine obesity. In people, tissues develop insulin resistance with excessive caloric intake. Plasma concentrations of insulin also increase in direct proportion to increasing BMI in men and women. Abdominal obesity is a major determinant of insulin resistance, hyperinsulinemia, and, subsequently, type-2 diabetes mellitus in people.10,47,48 In people, metabolic syndrome is a group of risk factors associated with insulin resistance, cardiovascular disease, and inflammation.4,49 Canine diabetic patients commonly suffer from diabetes mellitus resembling human type-1 diabetes mellitus. Since type-2 diabetes mellitus is uncommon in dogs, obesity rarely leads to overt clinical signs of diabetes mellitus.46
Although hypothyroidism is commonly considered an underlying cause of obesity, such cases are relatively unusual.50 While hypothyroidism should always be a differential diagnosis in obese dogs, it is rarely the sole cause. Obese dogs have marginally higher concentrations of both total T4 and total T3 concentrations than nonobese dogs do, but free T4 concentrations, thyroid stimulating hormone (TSH) concentrations, and TSH stimulation test results are not significantly different.51,52 Thus, although obesity may have some effect on thyroid homeostasis, such changes are unlikely to affect the interpretation of thyroid function tests.
Hyperadrenocorticism has been associated with increased intra-abdominal adipose deposition. Combined with the weakening of ventral abdominal musculature secondary to endogenous corticosteroids, patients living with this condition certainly may be readily classified as overweight or obese.53,54
In experimental models, obese dogs had mild elevations in cholesterol, triglyceride, and phospholipid concentrations compared with normal-weight dogs.29,55 Laboratory dogs that had been made obese had increased total cholesterol concentrations and increased cholesterol concentrations in very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) fractions. Additionally, these dogs had higher triglyceride concentrations in total plasma and in the VLDL fractions. These dyslipidemic changes were associated with insulin resistance after lipid infusion.29,55
Orthopedic diseases, including osteoarthritis, osteochondrosis, and osteochondritis dissecans, are the most common obesity-associated problems in dogs.56,57 A recent study demonstrated food intake may have a significant effect on the development of osteoarthritis in dogs, and the disease severity was associated with unrestricted feeding.58
Cardiopulmonary disease and hypertension
Obesity may have a marked effect on respiratory function and is a recognized risk factor for the development of tracheal collapse in small-breed dogs.59 Other respiratory diseases frequently exacerbated by obesity include laryngeal paralysis, asthma, and brachycephalic airway obstruction syndrome; obstruction of thoracic movement related to obesity hypoventilation syndrome (also known as Pickwickian-type syndrome) also occurs.60-63 Obesity hypoventilation syndrome in people is defined as obesity accompanied by lethargy, drowsiness, hypoventilation, hypoxia, and secondary polycythemia.
Obesity may also affect arterial blood pressure in pets, as hypertension has been reported in 23% to 45% of obese dogs.12,64 One study showed that 67% of obese dogs had a systolic blood pressure > 160 mm Hg and that obese dogs had significantly higher blood pressure than control dogs did.65 Hypertension was considered a risk factor associated with BCS in dogs.
Obesity in people reduces systolic and diastolic functions of both the left and right ventricles, and the severity of the dysfunction is related to the magnitude of obesity.66-68 Research has also shown that overweight dogs without overt heart disease have preclinical left myocardial systolic and diastolic function changes.69 Thus, even without a predisposition to ischemic heart disease, obesity has an impact on ventricular function in dogs.
An association between obesity and some cases of urethral sphincter mechanism incompetence has been reported.70 Indeed, weight reduction in overweight dogs with urethral sphincter mechanism incompetence is often all that is required to restore continence. Although the mechanism is not clear, one possible explanation is that increased retroperitoneal fat may lead to caudal displacement of the urinary bladder. Obese animals are reported to suffer from an increased risk of dystocia,71 likely related to excess adipose tissue in and around the birth canal.
Obesity is known to predispose people to various types of neoplasia, including breast, colorectal, renal cell, and esophageal cancer.8 Recent epidemiologic evidence from dogs and cats suggests overweight and obese animals have an increased risk of developing neoplasia.12 Further, overweight dogs reportedly have an increased risk of developing transitional cell carcinoma of the bladder.72
A limited number of retrospective studies have evaluated the correlation between specific cancer types and obesity prevalence in dogs. A large retrospective study of dogs presenting to a referral veterinary teaching hospital showed a lower prevalence of obesity among dogs when all types of malignant neoplasia were evaluated together but a difference in obesity prevalence when cancer types were evaluated individually and compared with dogs without cancer.72
Researchers in one study collected owner-reported obesity statuses a year before the dogs were diagnosed with transitional cell carcinoma of the urinary bladder and found that dogs exposed to topical insecticide use had an increased risk of developing bladder cancer and that this risk was increased in overweight or obese dogs compared with size- and age-matched control dogs that had other neoplasms or chronic diseases.73 Other studies showed a positive correlation between mammary tumor development and owner-reported obesity.73-75 Another study found a higher prevalence of overweight or obese dogs with mammary cancers compared with dogs without cancer.72 Conversely, another study found no correlation with obesity and mammary tumor development.76
Mortality data from a long-term prospective study on calorie restriction showed an equal distribution of cancers among 24 pairs of control and restricted-fed Labrador retrievers.46 The variety of cancer types reported, limited sample size, and avoidance of overt obesity in control dogs make direct conclusions about obesity and cancer development in that study difficult.
Adipocytes' ability to secrete cytokines and inflammatory markers into the circulation has been well-documented in people and domestic animal species. Proteins including leptin, adiponectin, and retinol-binding protein can induce peripheral insulin-resistance, inhibit normal apoptotic mechanisms, promote angiogenesis, and decrease circulating HDL concentrations in people. As such, chronic inflammation associated with obesity has been proposed to result in oxidative injury to DNA and predispose obese people to increased cancer risk.77
Obese dogs have increased circulating concentrations of adipokines, such as insulin-like growth factor, tumor necrosis factor-alpha, and leptin.47 Leptin is an in vitro promoter of mammary tumors and hepatocellular carcinomas in people.78 To date, this relationship has not been documented in dogs. Tumor suppressor genes, such as p53, are found in about half of all cancers in people and in certain canine cancers, such as mammary tumors and osteosarcoma.79-82 Elevated leptin concentrations can directly inhibit p53 expression in human mammary cancer cells in vitro.83
A number of techniques for evaluating canine weight and body composition have been examined in recent years. These include deuterium oxide dilution, bioelectrical impedance, ultrasonography, dual-energy X-ray absorptiometry, and BCS.84-87 For field purposes, BCS is a simple, expedient, noninvasive, and invaluable tool for assessing obesity during a complete physical examination.88 BCS provides a subjective yet quantitative way to estimate the amount of excess adipose tissue present. A validated, nine-point system is a commonly used method for assessing BCS in which each point is 10% to 15% of body weight. Overweight in dogs is defined as a BCS of 6/9 or 7/9. Canine obesity is defined, as in people, as weighing about 30% or more over ideal (equivalent to a BCS 8/9 or 9/9).89
By recording both body weight and BCS, ideal body weight may be more easily determined through serial monitoring of trends in these measures.90 Patients that are overweight will be recognized sooner, as will contributing factors, such as endocrinopathies, and associated problems, such as hyperlipidemia. Quantifying body condition also facilitates communication with clients—an important aspect of weight control.
Dogs become overweight or obese because of a combination of causes with physical, emotional (owner-related), environmental, endocrine, or neurologic components. Musculoskeletal problems and developmental abnormalities may also greatly influence a dog's ability to exercise and may ultimately contribute to weight gain. Indiscriminate feeding habits including feeding table scraps, poor diet, and constant access to food are significant contributing factors to this most prevalent issue in the canine population.
Christopher G. Byers, DVM, DACVECC, DACVIM
VCA Veterinary Referral Associates
500 Perry Parkway
Gaithersburg, MD 20877
Cindy C. Wilson, PhD
Mark B. Stephens, MD, MS
Jeffrey Goodie, PhD, ABPP
Department of Family Medicine
School of Medicine Uniformed Services
University of the Health Sciences
Bethesda, MD 20814
F. Ellen Netting, PhD
School of Social Work
Virginia Commonwealth University
Richmond, VA 23284
Cara Olsen, PhD
Department of Preventive Medicine and Biometrics
School of Medicine Uniformed Services
University of the Health Sciences
Bethesda, MD 20814
1. Cheitlin MD. Obesity is bad: but what should the definition be, and when is it bad? Cardiol Rev 2001;9:208-209.
2. Polk SL. Definitions and demographics of obesity: diagnosis and risk factors. Anesthesiol Clin North Am 2005;23:397-403, v.
3. Donath SM. Who's overweight? Comparison of the medical definition and community views. Med J Aust 2000;172:375-377.
4. Etemadi A, Malekzadeh R. Definition and etiology of metabolic syndrome. Arch Iran Med 2008;11:1-2.
5. Garcia-Marcos L, Valverde-Molina J, Ortega ML, et al. Percent body fat, skinfold thickness or body mass index for defining obesity or overweight, as a risk factor for asthma in schoolchildren: which one to use in epidemiological studies? Matern Child Nutr 2008;4:304-310.
6. James WP. The epidemiology of obesity. Ciba Found Symp 1996;201:1-11; discussion 11-16, 32-36.
7. Bach JF, Rozanski EA, Bedenice D, et al. Association of expiratory airway dysfunction with marked obesity in healthy adult dogs. Am J Vet Res 2007;68:670-675.
8. Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J Pathol 2006;169:1505-1522.
9. Martin LJ, Siliart B, Dumon HJ, et al. Hormonal disturbances associated with obesity in dogs. J Anim Physiol Anim Nutr (Berl) 2006;90:355-360.
10. Zou C, Shao J. Role of adipocytokines in obesity-associated insulin resistance. J Nutr Biochem 2008;19:277-286.
11. Mason E. Obesity in pet dogs. Vet Rec 1970;86:612-616.
12. Gossellin J, Wren JA, Sunderland SJ. Canine obesity: an overview. J Vet Pharmacol Ther 2007;30(Suppl 1):1-10.
13. Colliard L, Ancel J, Benet JJ, et al. Risk factors for obesity in dogs in France. J Nutr 2006;136:1951S-1954S.
14. McGreevy PD, Thomson PC, Pride C, et al. Prevalence of obesity in dogs examined by Australian veterinary practices and the risk factors involved. Vet Rec 2005;156:695-702.
15. Edney AT, Smith PM. Study of obesity in dogs visiting veterinary practices in the United Kingdom. Vet Rec 1986;118:391-396.
16. Crane SW. Obesity treatment and prevention in companion animals. Tijdschr Diergeneeskd 1992;117(Suppl 1):44S-45S.
17. Kronfeld DS, Donoghue S, Glickman LT. Body condition and energy intakes of dogs in a referral teaching hospital. J Nutr 1991;121(11 Suppl):S157-S158.
18. German AJ. The growing problem of obesity in dogs and cats. J Nutr 2006;136 (7 Suppl):1940S-1946S.
19. Roberts SB, Greenberg AS. The new obesity genes. Nutr Rev 1996;54:41-49.
20. Eisele I, Wood IS, German AJ, et al. Adipokine gene expression in dog adipose tissues and dog white adipocytes differentiated in primary culture. Horm Metab Res 37:474-481.
21. Leray V, Serisier S, Khosniat S, et al. Adipose tissue gene expression in obese dogs after weight loss. J Anim Physiol Anim Nutr (Berl) 2008;92:390-398.
22. Armstrong J, Lund EM. Obesity: research update, in Proceedings. Petfood Forum 1997 (available from Watts Publishing).
23. Meyer H, Drochner W, Weidenhaupt C. [A contribution to the occurrence and treatment of obesity in dogs]. Dtsch Tierarztl Wochenschr 1978;85:133-136.
24. Diez M, Nguyen P. The epidemiology of canine and feline obesity. Waltham Focus 2006;16:2-8.
25. Armstrong JP, Lund EM. Changes in body composition and energy balance with aging. Vet Clin Nutr 1996;3:83-87.
26. Laflamme DP, Ballam JM. Effect of age on maintenance energy requirements of adult cats. Compend Contin Edu Pract Vet 2002;24(Suppl 9A):82.
27. Robertson ID. The association of exercise, diet and other factors with owner-perceived obesity in privately owned dogs from metropolitan Perth, WA. Prev Vet Med 2003;58:75-83.
28. Jeusette I, Detilleux J, Cuvelier C, et al. Ad libitum feeding following ovariectomy in female Beagle dogs: effect on maintenance energy requirement and on blood metabolites. J Anim Physiol Anim Nutr (Berl) 2004;88:117-121.
29. Jeusette IC, Lhoest ET, Istasse LP, et al. Influence of obesity on plasma lipid and lipoprotein concentrations in dogs. Am J Vet Res 2005;66:81-86.
30. Houpt KA, Coren B, Hintz HF, et al. Effect of sex and reproductive status on sucrose preference, food intake, and body weight of dogs. J Am Vet Med Assoc 1979;174:1083-1085.
31. Jeusette I, Daminet S, Nguyen P, et al. Effect of ovariectomy and ad libitum feeding on body composition, thyroid status, ghrelin and leptin plasma concentrations in female dogs. J Anim Physiol Anim Nutr (Berl) 2006;90:12-18.
32. Axelsson J, Heimburger O, Lindholm B, et al. Adipose tissue and its relation to inflammation: the role of adipokines. J Ren Nutr 2005;15:131-136.
33. Bulcao C, Ferreira SR, Giuffrida FM, et al. The new adipose tissue and adipocytokines. Curr Diabetes Rev 2006;2:19-28.
34. Radin MJ, Sharkey LC, Holycross BJ. Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses. Vet Clin Pathol 2009;38:136-156.
35. Badman MK, Flier JS. The adipocyte as an active participant in energy balance and metabolism. Gastroenterology 2007;132:2103-2115.
36. Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006;444:847-853.
37. Juge-Aubry CE, Henrichot E, Meier CA. Adipose tissue: a regulator of inflammation. Best Pract Res Clin Endocrinol Metab 2005;19:547-566.
38. Lago F, Dieguez C, Gomez-Reino J, et al. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 2007;3:716-724.
39. Goldstein BJ, Scalia R. Adiponectin: A novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 2004;89:2563-2568.
40. Pan W, Kastin AJ. Adipokines and the blood-brain barrier. Peptides 2007;28:1317-1330.
41. Bland IM, Guthrie-Jones A, Taylor RD, et al. Dog obesity: owner attitudes and behaviour. Prev Vet Med 2009;92:333-340.
42. Burkholder WJ, Bauer JE. Foods and techniques for managing obesity in companion animals. J Am Vet Med Assoc 1998;212:658-662.
43. Courcier E, Thomson R, Mellor D, et al. Canine obesity: do owners see what you see? in Proceedings. Br Sm Anim Vet Cong, 2009.
44. Vuorela N, Saha MT, Salo MK. Parents underestimate their child's overweight. Acta Paediatr 2010;99:1374-1379.
45. Courcier EA, Thomson RM, Mellor DJ, et al. An epidemiological study of environmental factors associated with canine obesity. J Small Anim Pract 2010;51(7):362-367.
46. Lawler DF, Evans RH, Larson BT, et al. Influence of lifetime food restriction on causes, time, and predictors of death in dogs. J Am Vet Med Assoc 2005;226:225-231.
47. Gayet C, Bailhache E, Dumon H, et al. Insulin resistance and changes in plasma concentration of TNFalpha, IGF1, and NEFA in dogs during weight gain and obesity. J Anim Physiol Anim Nutr (Berl) 2004;88:157-165.
48. Gayet C, Leray V, Saito M, et al. The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-gamma target genes, in dogs. Br J Nutr 2007;98:497-503.
49. Pi-Sunyer X. The metabolic syndrome: how to approach differing definitions. Med Clin North Am 2007;91:1025-1040, vii.
50. Dixon RM, Reid SW, Mooney CT. Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism. Vet Rec 1999;145:481-487.
51. Bensaid M, Gary-Bobo M, Esclangon A, et al. The cannabinoid CBI receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 2003;63:908-914.
52. Daminet S, Jeusette I, Duchateau L, et al. Evaluation of thyroid function in obese dogs and in dogs undergoing a weight loss protocol. J Vet Med A Physiol Pathol Clin Med 2003;50:213-218.
53. Reusch CE. Hyperadrenocorticism. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. Philadelphia, Pa: Saunders, 2005;1592-1610.
54. Feldman EC, Nelson RW. Canine and feline endocrinology & reproduction. 3rd ed. Philadelphia, Pa: Saunders, 2004;252-353.
55. Chiu JD, Kolka CM, Richey JM, et al. Experimental hyperlipidemia dramatically reduces access of insulin to canine skeletal muscle. Obesity (Silver Spring) 2009;17:1486-1492.
56. Lauten SD. Nutritional risks to large-breed dogs: from weaning to the geriatric years. Vet Clin North Am Small Anim Pract 2006;36:1345-1359, viii.
57. Huck JL, Biery DN, Lawler DF, et al. A longitudinal study of the influence of lifetime food restriction on development of osteoarthritis in the canine elbow. Vet Surg 2009;38:192-198.
58. Kealy RD, Lawler DF, Ballam JM, et al. Evaluation of the effect of limited food consumption on radiographic evidence of osteoarthritis in dogs. J Am Vet Med Assoc 2000;217:1678-1680.
59. White RAS, Williams, JM. Tracheal collapse in the dog—is there really a role for surgery? A survey of 100 cases. J Small Anim Pract 1994;35(4):191-196.
60. Panciera DL. Conditions associated with canine hypothyroidism. Vet Clin North Am Small Anim Pract 2001;31:935-950.
61. Bruchim Y, Klement E, Saragusty J, et al. Heat stroke in dogs: a retrospective study of 54 cases (1999-2004) and analysis of risk factors for death. J Vet Intern Med 2006;20:38-46.
62. Sin DD, Sutherland ER. Obesity and the lung: 4. Obesity and asthma. Thorax 2008;63:1018-1023.
63. Johnston RA, Theman TA, Lu FL, et al. Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation. J Appl Physiol 2008;104:1727-1735.
64. Bland IM, Guthrie-Jones A, Taylor RD, et al. Dog obesity: veterinary practices' and owners' opinions on cause and management. Prev Vet Med 2010;94:310-315.
65. Joles JA. Obesity in dogs: effects on renal function, blood pressure, and renal disease. Vet Q 1998;20:117-120.
66. Behn A, Ur E. The obesity epidemic and its cardiovascular consequences. Curr Opin Cardiol 2006;21:353-360.
67. Pelat M, Verwaerde P, Lazartiques E, et al. [Twenty-four hour time and frequency domain variability of systolic blood pressure and heart rate in an experimental model of arterial hypertension plus obesity]. Arch Mal Coeur Vaiss 1998;91:999-1002.
68. Massabuau P, Verwaerde P, Galinier M, et al. [Left ventricular repercussion of obesity-induced arterial hypertension in the dog]. Arch Mal Coeur Vaiss 1997;90:1033-1035.
69. Verwaerde P, Senard JM, Galinier M, et al. Changes in short-term variability of blood pressure and heart rate during the development of obesity-associated hypertension in high-fat fed dogs. J Hypertens 1999;17:1135-1143.
70. Gregory SP. Developments in the understanding of the pathophysiology of urethral sphincter mechanism in competence in the bitch. Br Vet J 1994;150:135-150.
71. Sanderson S. Canine obesity management: traditional and new approaches, in Proceedings. Am Coll Vet Intern Med Forum, 2009.
72. Weeth LP, Fascetti AJ, Kass PH, et al. Prevalence of obese dogs in a population of dogs with cancer. Am J Vet Res 2007;68:389-398.
73. Glickman LT, Schofer FS, McKee LJ, et al. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J Toxicol Environ Health 1989;28:407-414.
74. Sonnenschein EG, Glickman LT, Goldschmidt MH, et al. Body conformation, diet, and risk of breast cancer in pet dogs: a case-control study. Am J Epidemiol 1991;133:694-703.
75. Perez Alenza D, Rutteman GR, Pena L, et al. Relation between habitual diet and canine mammary tumors in a case-control study. J Vet Intern Med 1998;12:132-139.
76. Philibert JC, Snyder PW, Glickman N, et al. Influence of host factors on survival in dogs with malignant mammary gland tumors. J Vet Intern Med 2003;17:102-106.
77. Cottam DR, Mattar SG, Barinas-Mitchell E, et al. The chronic inflammatory hypothesis for the morbidity associated with morbid obesity: implications and effects of weight loss. Obes Surg 2004;14:589-600.
78. Wang XJ, Yuan SL, Lu Q, et al. Potential involvement of leptin in carcinogenesis of hepatocellular carcinoma. World J Gastroenterol 2004;10:2478-2481.
79. Lee CH, Kweon OK. Mutations of p53 tumor suppressor gene in spontaneous canine mammary tumors. J Vet Sci 2002;3:321-325.
80. Johnson AS, Couto CG, Weghorst CM. Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog. Carcinogenesis 1998;19:213-217.
81. Chang F, Syrjanen S, Tervahauta A, et al. Tumourigenesis associated with the p53 tumour suppressor gene. Br J Cancer 1993;68:653-661.
82. Berrigan D, Perkins SN, Haines DC, et al. Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis 2002;23:817-822.
83. Chen C, Chang YC, Liu CL, et al. Leptin-induced growth of human ZR-75-1 breast cancer cells is associated with up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21WAF1/CIP1. Breast Cancer Res Treat 2006;98:121-132.
84. German AJ, Holden SL, Moxham GL, et al. A simple, reliable tool for owners to assess the body condition of their dog or cat. J Nutr 2006;136(7 Suppl):2031S-2033S.
85. Ishioka K, Okumura M, Sagawa M, et al. Computed tomographic assessment of body fat in beagles. Vet Radiol Ultrasound 2005;46:49-53.
86. Mawby DI, Bartges JW, d'Avignon A, et al. Comparison of various methods for estimating body fat in dogs. J Am Anim Hosp Assoc 2004;40:109-114.
87. Stone R, Berghoff N, Steiner J, et al. Use of a bioelectric impedance device in obese and lean healthy dogs to estimate body fat percentage. Vet Ther 2009;10:59-70.
88. Dorsten CM, Cooper DM. Use of body condition scoring to manage body weight in dogs. Contemp Top Lab Anim Sci 2004;43:34-37.
89. Laflamme DP. Development and validation of a body condition score system for dogs: a clinical tool. Canine Pract 1997;22:10-15.
90. German AJ, Holden SL, Bissot T, et al. Use of starting condition score to estimate changes in body weight and composition during weight loss in obese dogs. Res Vet Sci 2009;87:249-254.