Obesity as an endocrine disease (Proceedings)

Obesity is at epidemic proportions in the United States and worldwide. Despite major public health initiatives spanning several decades, human obesity has reached prevalence rates nearing 40% in some states. Obesity in dogs and cats has followed this trend. Obesity is loosely defined as body weight 20% above the ideal, or as accumulation of body fat to the extent that it affects the animal's health.

Risk factors for obesity

There are several risk factors for obesity in dogs. These include breed (e.g., Labrador Retriever, Cairn Terrier, Cavalier King Charles Spaniel, Scottish Terrier, Cocker Spaniel); neutering; and several owner behavioral and socioeconomic factors. Owner factors include over-humanizing pets, owner obesity, time spent observing pet eating, and lower income. Interestingly, the type of food a dog is fed is not associated with obesity. A recent study showed that cats gained 40% of their body weight by being fed free-choice food for 3 months after spaying. To maintain pre-spay body weight, food intake had to be reduced by 30%. Similar studies have demonstrated increased obesity in neutered dogs as well. The simple reason for obesity is that energy intake exceeds energy expenditure. This can occur when a dog has excessive caloric intake (food and treats) or reduced energy expenditure (e.g., reduced activity, illness or injury resulting in less exercise).

Some medical conditions (endocrinopathies, such as hypercortisolism and hypothyroidism) and drugs (steroids and anticonvulsants) are associated with obesity. Medical conditions should be considered carefully in the clinical approach to an obese animal. Hypothyroidism is diagnosed commonly in dogs and is often suspected as a prime differential in obese dogs. This disease, however, is widely overdiagnosed, and owners are often frustrated when their dogs fail to lose weight despite thyroid hormone supplementation. Hypercortisolism (Cushing's syndrome), on the other hand, may be underdiagnosed. Glucocorticosteroid hormones, endogenous or exogenous, are known to cause increased body fat in many species, and it is important to consider this syndrome as a differential in obese dogs. While genetic factors are also probably involved in the predisposition of some breeds to obesity (e.g., Labrador retrievers have a higher incidence of obesity than is seen in other breeds of like size), the role of inheritance in canine obesity needs more study.

"[There is a] popular belief, particularly among lean individuals, that regulation of body weight is largely a matter of willpower. It is hard to imagine such a view of the regulation of any similarly important aspect of physiology, for example blood pressure, persisting for so long." -A.M. Wren and S.R. Bloom, Imperial College London, Gastroenterology 2007;132:2116-2130

Endocrinology of adipose tissue and obesity

Based on the current understanding of fat endocrinology, it is reasonable to consider obesity a true medical disorder rather than simply a lifestyle/willpower issue. Fat is an endocrine organ that secretes a variety of hormones and cytokines.3 These are collectively termed "adipokines." Leptin and adiponectin are the best characterized fat-derived hormones. Leptin is important in regulation of energy balance and satiety. Leptin concentrations in the circulation increase in obesity, but this is because of leptin resistance, so the beneficial effects of leptin are lost. Adiponectin is a hormone with several functions, but the most important is probably in conferring insulin sensitivity. As body fat increases, adiponectin concentrations drop, contributing to the insulin resistance of obesity. The effects of adiponectin and leptin have been documented in dogs. Other hormones secreted by fat cells include resistin and vistatin, which are involved in insulin resistance, and apelin, which may contribute to hypertension in obesity. These hormones have not been well-studied in dogs and cats. Vistatin affects insulin secretion.

In addition to hormones, inflammatory cytokines are secreted by adipose tissue. Abnormally increased concentrations of adipose-derived tumor necrosis factor-alpha, for example, provides an illustration of obesity as a systemic inflammatory condition.

Other proinflammatory adipokines are present in obesity as well.

Gut-derived hormones, which are critical for appetite control and glucose homeostasis, are also abnormal during obesity.7 In particular, ghrelin, a powerful orexigenic hormone secreted by the gastrointestinal tract, remains elevated longer post-prandially in obese human patients, although studies of this effect have not been reported in dogs or cats. As a result of ghrelin dysregulation, obese patients need less food but are more hungry, illustrating the vicious cycle of obesity and loss of appetite control.

In addition to the abnormal endocrine functions of adipose tissue itself, other endocrine systems are affected by obesity. Increased serum thyroid hormone concentrations, believed to reflect thyroid hormone resistance, have been documented in canine obesity, as have increases in circulating concentrations of prolactin, insulin, and insulin-like growth factor 1. Obese dogs secrete more cortisol in response to ACTH stimulation than do lean dogs, further illustrating the multisystemic nature of the medical disorder of obesity.

Obesity-associated disease

Obese human beings generally do not live as long as their lean counterparts and are much more prone to such diseases as type 2 diabetes, coronary artery disease, osteoarthritis, hypertension, and some types of cancer. Obese dogs and cats are susceptible to the same detrimental effects, including decreased lifespan and development of a variety of disorders. This was best illustrated in a study of two groups of Labrador Retrievers, in which one group had a 25% lifelong reduction in caloric intake compared with the other group. In that study, dogs fed less food were leaner and significantly outlived the other dogs. In addition, incidence of osteoarthritis and hip dysplasia was decreased, and glucose tolerance was improved in the food-restricted group.

There are numerous other obesity-related diseases in dogs and cats—some are caused by obesity and others are exacerbated by it. Such disorders include orthopedic diseases, lipid disorders, diabetes, urinary incontinence, and a variety of respiratory disorders. Even some types of neoplasia have been strongly associated with obesity in dogs. Veterinarians are familiar with the dramatic decline in the incidence of mammary cancer resulting from ovariohysterectomy in bitches, but that protective effect is often lost as a result of obesity. Obesity has also been established as a risk factor for transitional cell carcinoma in dogs.

Weight loss: obstacles and strategies

Weight loss can be difficult in veterinary patients. Successful weight loss requires either decreasing energy intake or increasing metabolism—usually both are required. Increasing energy expenditure can be hampered by musculoskeletal problems associated with obesity, or by the pet owner's lifestyle. Decreasing the amount of food given to an obese dog can also be difficult. Most pet owners find their pets' food-seeking behavior hard to resist.

Another challenge to weight loss is the irreversible increase in the number of adipocytes associated with obesity. During obesity adipocytes increase in size, but they also increase in number. During weight loss, the size of adipocytes decreases, but the increased number of cells remains unchanged

Recently, a new pharmaceutical approach to canine obesity has been used. Dirlotapide is a drug that increases release of peptide YY, a powerful centrally acting appetite suppressant, from intestinal cells following a meal. When used in dogs, dirlotapide significantly decreases appetite and is associated with significant weight loss. When prescribing dirlotapide, it is important to have careful case follow-up to ensure compliance and to monitor weight loss. Drug dosages are adjusted to maintain a slow, steady rate of weight loss.

One of the most important obstacles to weight loss in the dog may be owners attitudes. We have begun collecting data for a study of owner awareness and attitudes towards obesity in dogs and cats in Chicago. Many studies have demonstrated the phenomenon of erroneous weight perception on the part of parents of obese children. Although some studies have shown that parents of obese children are sometimes able to identify them as overweight, the majority of parents fail to perceive obesity in their children. This is especially true with younger children and weight misperception is also affected by certain cultural and socio-economic factors. We hypothesize that owners fail to perceive obesity in their pets, and there is a lack of concern for the health consequences of obesity in their pets. To test this hypothesis, we are comparing owner perception of a pet's body condition with assessment of body condition performed by a veterinarian skilled in body condition scoring. We seek to determine if pet owners perceive any adverse health risks associated with obesity in their pets. We are also investigating the effects of owner gender, sex of the pet, age, and pet breed on accuracy of weight perception. While the study is not yet completed and the data not fully analyzed, we have enrolled large numbers of study subjects, and the preliminary data indicate that pet owners are no better at recognizing obesity or excess body weight in their animals than are parents of obese children. Our preliminary results seem to indicate that even when pet owners recognize obesity, they may not be concerned about the effects of obesity on their pets' health. This means that veterinarians have a serious challenge in approaching the topic of pet obesity with their clients. It is important to find ways to help owners recognize the scope of the problem and the consequences of obesity.

One tool that could help pet owners recognize the impact of obesity on their pets' health could be the development of clinical tests to quantify the deleterious effects of excess body fat. Biomarkers for obesity-related health problems are a current topic of interest among veterinary nutrition researchers. Measurement of adipokines, lipids, inflammatory mediators, and other molecules associated with obesity could be used to identify co-morbidities in obese dogs. Biomarkers could also be used to identify patients at risk for obesity-related problems or for the development of obesity, and they could have value in monitoring response to therapy for obesity. Panels of obesity biomarkers are currently available for use in human and rodent obesity research, but have not been applied extensively to clinical work in obese patients.

References

Kealy RD, Lawler DF, Ballam JM, Mantz SL, Biery DN, Greeley EH, Lust G, Segre M, Smith GK, Stowe HD. Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc. 2002;220:1315-1320.

Kienzle E, Bergler R, Mandernach A.A comparison of the feeding behavior and the human-animal relationship in owners of normal and obese dogs. J Nutr. 1998 Dec;128(12 Suppl):2779S-2782S. No abstract available.

Belsito KR, Vester BM, Keel T, Graves TK, Swanson KS. Impact of ovariohysterectomy and food intake on body composition, physical activity, and adipose gene expression in cats. J Anim Sci. 2009;87:594-602

Vázquez-Vela ME, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res. 2008;39:715-728

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.

Ishioka K, Omachi A, Sagawa M, et al. Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity. Res Vet Sci. 2006;80:127-132.

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.

Wren AM, Bloom SR.Gut hormones and appetite control. Gastroenterology. 2007;132:2116-2130. Review.

Erdmann J, Leibl M, Wagenpfeil S, Lippl F, Schusdziarra V. Ghrelin response to protein and carbohydrate meals in relation to food intake and glycerol levels in obese subjects. Regul Pept. 2006;135:23-29. Epub 2006 Apr 27.

Yamka RM, Friesen KG, Frantz NZ. Identification of canine markers related to obesity and the effects of weight loss on the markers of interest. Intern J Appl Res Vet Med. 2006;4:282-292.

Martin LJM, Siliart B, Dumon HJW, et al. Hormonal disturbance associated with obesity in dogs. J Anim Physiol Anim Nutr. 2006;90:355-360.

Gayet C, Bailhache E, Dumon H, et al. Insulin resistance and changes in plasma concentration of TNF, IGF-1, and NEFA in dogs during weight gain and obesity. J Anim Physiol Anim Nutr. 2004;88:157-165.

Sonnenschein EG, Glickman LT, Goldschmidt MH, McKee LJ. Body conformation, diet, and risk of breast cancer in pet dogs: a case-control study. Am J Epidemiol. 1991;133:694-703.

Glickman LT, Schofer FS, McKee LJ, Reif JS, Goldschmidt MH. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J Toxicol Environ Health. 1989;28:407-414.

Wren JA, Ramudo AA, Campbell SL, et al. Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America. J Vet Pharmacol Ther. 2007;30[Suppl 1]:81-89.

Vuorela N, Saha MT, Salo MK. Parents underestimate their child`s overweight. Acta Paediatr. 2010 Sep;99(9):1374-9

Etelson D, Brand DA, Patrick PA, Shirali A. Childhood Obesity: Do Parents Recognize This Health Risk? Obesity Research (2003) 11, 1362–1368;

Eckstein KC, Mikhail LM, Ariza AJ, Thomson JS, Millard SC, Binns HJ. Parents' Perceptions of Their Child's Weight and Health. PEDIATRICS Vol. 117 No. 3 March 2006, pp. 681-690

Doolen J, Alpert PT, Miller SK. Parental disconnect between perceived and actual weight status of children: a metasynthesis of the current research. J Am Acad Nurse Pract. 2009 Mar;21(3):160-6.

Júlíusson PB, Roelants M, Markestad T, Bjerknes R. Parental perception of overweight and underweight in children and adolescents. Acta Paediatr. 2010 Oct 1. doi: 10.1111/j.1651-2227.2010.02039.x.

Rudolph H, Blüher S, Falkenberg C, Neef M, Körner A, Würz J, Kiess W, Brähler E. Perception of body weight status: a case control study of obese and lean children and adolescents and their parents. Obes Facts. 2010;3(2):83-91.

Jimenez-Cruz A, Bacardi-Gascon M, Castillo-Ruiz O, Mandujano-Trujillo Z, Pichardo-Osuna A. Low income, Mexican mothers' perception of their infants' weight status and beliefs about their foods and physical activity. Child Psychiatry Hum Dev. 2010 Oct;41(5):490-500.

Guendelman S, Fernald LC, Neufeld LM, Fuentes-Afflick E. Maternal perceptions of early childhood ideal body weight differ among Mexican-origin mothers residing in Mexico compared to California. J Am Diet Assoc. 2010 Feb;110(2):222-9.

Armstrong PJ. Are adipokines functional biomarkers of obesity? Proceedings of the Companion Animal Nutrition Summitt: Focus on Obesity and Obesity-related Diseases, Tucson, AZ, 2011, pp.26-32.