Obesity: Health and mobility risks (Sponsored by Iams)

Obesity is the most common nutritional disorder in dogs. A 1986 study estimated the prevalence of canine obesity to be 24%,1 and a similar 2005 study estimated the incidence of obesity to be 41%.2 About 50% of dogs in the United States between the ages of 5 and 10 years are overweight or obese.3

Along with this increase in pet obesity comes an increase in obesity-associated health problems. Health problems caused or complicated by obesity include:

• Decreased life expectancy

• Reduced quality of life

• Chronic inflammation

• Joint/musculoskeletal problems and osteoarthritis

• Pulmonary and cardiovascular disease

• Exercise and heat intolerance

• Compromised immune function

• Pancreatitis

• Increased morbidity and mortality during and after anesthesia (many anesthetics are fat soluble, so recovery may take longer).

White adipose tissue: A major endocrine organ

For many years, white adipose tissue (WAT) was considered metabolically inert. Its primary role in disease was attributed to the effects of increased weight bearing causing stress on joints and increased cardiac workload. However, our understanding of WAT's physiologic role changed in 1994 with the discovery of a hormone, leptin, which is produced predominantly by WAT.4 Since that discovery, numerous other protein signals and factors, called adipokines, have been shown to be secreted by WAT. As a result, WAT is no longer viewed simply as a vehicle for storage and release of fatty acids. Instead, WAT is recognized as a major endocrine organ and signaling tissue, which interacts extensively with other organs in overall physiologic and metabolic control. Two of these important adipokines secreted by adipose tissue are leptin and adiponectin.

Leptin

The hormone leptin plays a key role in regulating energy balance. Leptin is constitutively secreted by adipocytes, and its transcriptional regulation depends on energy flux within adipocytes. Leptin stimulates energy expenditure (thermogenesis) to help balance the effects of excessive caloric intake. In addition, leptin's release from adipose tissue is a key trigger for the hypothalamus that results in decreased appetite and reduced food intake in normally responsive, nonobese individuals.5

In people and rodents, plasma leptin concentrations are highly correlated with body mass index, and most obese individuals have high levels of plasma leptin. This increase in leptin associated with obesity is partly due to an increase in the amount of leptin-secreting adipose tissue.6 Furthermore, as the leptin level increases, it induces leptin resistance in target cells and interferes with the normal feedback in the hypothalamus that downregulates food intake. As a result, leptin becomes ineffective at controlling food intake, a condition known as leptin resistance. A similar obesity-associated increase in plasma leptin occurs in dogs, and the greater the degree of obesity, the higher the plasma leptin levels.7-9 In a study by Ishioka and colleagues,7 dogs with a body condition score (BCS) of 3/5 had mean plasma leptin levels of 3.0 ± 0.4 ng/ml; dogs with a BCS of 4/5 had mean plasma leptin levels of 8.6 ± 0.7 ng/ml; and dogs with BCS of 5/5 had mean plasma leptin levels of 12.8 ± 0.8 ng/ml. Therefore, plasma leptin is a good index of adiposity in dogs, as it is in people and rodents.

Leptin also alters cytokine production by immune cells, and transcription of leptin is increased by proinflammatory cytokines, such as tumor necrosis factoralpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6).10 As a result, leptin appears to be proinflammatory and may contribute to oxidative injury.

Adiponectin

Adiponectin—also called adipoQ, apM1, Acrp30, and GBP28—is specifically and very highly expressed in WAT. It plays an important role in regulating energy homeostasis, increasing insulin sensitivity, and has anti-inflammatory properties. In nonobese individuals, insulin stimulates adiponectin secretion by fat cells, which in turn suppresses hepatic glucose production,11 and increases fatty acid metabolism, thereby ameliorating insulin resistance.12 In skeletal muscle, adiponectin increases fatty acid metabolism and increases glucose uptake. These effects of adiponectin in the liver and skeletal muscle increase insulin sensitivity, reduce blood glucose levels, and decrease tissue triglyceride content. Adiponectin also suppresses TNF-α production by macrophages, thus exhibiting anti-inflammatory properties.13 In contrast, the production of reactive oxygen species and proinflammatory cytokines, such TNF-α and IL-6, associated with increasing adiposity inhibits adiponectin gene expression and secretion.14,15

In contrast to leptin, increases in fat mass decrease circulating adiponectin levels,16,17 while weight loss increases adiponectin concentrations in people,18 primates,19 and rodents.20 Adiponectin levels are also inversely related to adiposity in dogs; increasing adiposity decreases circulating levels of adiponectin.

The role of obesity in chronic health problems

Since WAT was recognized as an important endocrine org researchers have isolated more than 50 adipokines and found that they are involved in a wide range of physiologic processes. In addition to its hormonal function, WAT secretes many adipokines that are involved with the interaction among adipose tissue, inflammation, and immunity. Because of this relationship, obesity is now recognized as a chronic inflammatory condition, and many obesity-related health problems are linked to this state of chronic inflammation.21-23 For example, persistent, low-grade inflammation and increased oxidative stress secondary to obesity may play a role in chronic diseases such as osteoarthritis (OA).

The association between obesity and OA

Obesity and OA are two significant health problems that affect dogs' health and quality of life, and OA is estimated to affect as many as 20% of dogs older than 1 year.24 A link between obesity and OA in people has been established. In people, obesity has been identified as a risk factor for the development of knee and hand OA and for the progression of knee OA.25-27 There is a growing body of evidence in human medicine to suggest that leptin has a detrimental effect on articular cartilage and plays a role in OA pathogenesis.28 Leptin also inhibits the long-term growth of cultured chondrocytes, and it induces production of interleukin-1 (IL-1), matrix metalloproteinase-13 (MMP-13), and MMP-9 in a dosedependent manner.29 This indicates that leptin has a catabolic effect on chondrocyte metabolism.

In dogs, there is also a relationship between obesity and OA. Although a clear cause-and-effect mechanism has not been found yet, some of the same processes occurring in people are likely occurring in dogs. A 13-year longitudinal lifespan study supports the fact that obesity increases the incidence of OA in dogs.30-33 In this study, 48 Labrador retrievers from seven litters were paired by sex and body weight. They were randomly and evenly divided into a control-fed group or a limit-fed group. The control-fed group was initially fed ad libitum, and then, at about 3 years, their intake was reduced to 62.1 kcal of metabolizable energy per kilogram of ideal body weight per day. The limit-fed group was fed 75% of the food consumed by the control-fed group.

At 12 years, the dogs in the control-fed group had a mean BCS of 6.7 out of 9, and the limit-fed group had a mean BCS of 4.6 out of 9. When compared with the control-fed group, the limit-fed group had a reduced incidence and severity of OA. There was also a delay in the need for treatment of OA in the limit-fed group. It is important to note that the control-fed group had a mean BCS of only 6.7 out of 9, so they were overweight but not obese. Had the dogs in the control-fed group had a BCS of 8 or 9, as many client-owned dogs do, the difference in the results might have been even more dramatic. Nonetheless, this study is important because it documented that excessive body weight not only increased the incidence of OA in dogs, but it also increased the severity. A number of mechanisms could account for these results. First, excessive weight increases the force on the joints and articular cartilage. Second, extra WAT results in the increased release of proinflammatory cytokines, which may worsen inflammation associated with OA.

The benefit of weight loss in OA management

In human medicine, there is strong evidence to support weight loss as a therapy for OA in obese individuals. One study showed that only a 5.1% reduction in body weight could significantly reduce self-reported disability in obese people with OA of the knee.34

There is also good evidence to support weight loss as a therapy for OA in obese dogs. In one study, 16 overweight and obese dogs with OA of the hips and a BCS of 6 to 8 out of 9 were evaluated using kinetic gait analysis.35 Weight loss that normalized the BCS (4 to 5 out of 9) significantly improved kinetic gait analysis results when compared with the baseline results. This study documented objective improvement in lameness from OA when overweight and obese dogs lost weight.

Another clinical study evaluated nine overweight dogs with lameness caused by OA.36 Lameness scores using a numerical rating and visual analogue scale showed that a 6.2% reduction in body weight could significantly improve subjective lameness scores.

A prospective clinical trial evaluated 29 dogs with lameness and OA in only one joint.37 These dogs had a BCS of 4 or 5 out of 5. The dogs were assigned subjective lameness and pain scores and underwent objective kinetic gait analysis before and after weight loss. In this study, weight loss was combined with either intense physiotherapy or moderate physiotherapy. The dogs in the intense physiotherapy weight loss group showed a greater improvement in lameness than those in the moderate physiotherapy weight loss group. Although it is difficult to determine what role weight loss versus physiotherapy had in improving the lameness, the study did show that the combination of therapies reduced disability in dogs with OA.

In a recent clinical study, 14 obese client-owned dogs with clinical and radiographic signs of OA in the hip or elbow or both were evaluated subjectively and objectively before and after weight loss.38 The only therapy the dogs received for their OA was weight loss. Weight loss decreased subjective clinical signs of lameness, and significant effects were seen with as little as 6.10% weight loss. Objective kinetic gait analysis results for obese dogs with elbow OA and forelimb lameness improved with as little as 8.85% weight loss. Therefore, even modest weight loss can result in significant improvement in obese dogs with OA. Therefore, weight loss should be considered an important component of both short- and long-term management of these patients. (For more on the role of weight loss in managing OA, see "Current concepts in the management of osteoarthritis".)

Managing canine obesity: A step-by-step approach

Weight-loss programs should have both short- and long-term goals. The short-term goal is for the patient to lose weight and reach its ideal BCS. The long-term goal is to keep the weight off once the weight-loss program is discontinued. Below are the steps to take, and the sidebar "Eppie: Successful weight loss with a step-by-step approach" demonstrates this method.

Step 1—Acknowledge that obesity is present.

Step 2—Obtain a thorough diet history from the owner.

Step 3—Form a partnership with the owner. For a weight-loss program to succeed, the client must accept the need for weight loss and be willing to perform the tasks to achieve the goal. Lifestyle changes are necessary for short- and long-term success, but it is important to maintain the owner-animal bond with any lifestyle change.

Step 4—Correct and control any underlying diseases.

Step 5—Induce a negative energy balance. The most effective way to induce a negative energy balance is to combine energy restriction with exercise. Exercise is an all too often forgotten component of a weight-loss program, but its beneficial effects on metabolic rate make it a critical component of any program.

Step 6—Calculate caloric requirements. Two methods can be used to calculate a starting point for caloric intake for an obesity management program. (See the Obesity Management Calculation Sheet.) Initial caloric calculations are only starting points; they may need to be modified based on a dog's response.

Obesity Management Calculation Sheet

Step 7—Choose an appropriate diet for weight loss. Most pet food companies that make therapeutic foods also make a weight-reduction food. Avoid starvation diets.

• Starvation diets restrict not just calories but every nutrient. Like people, dogs have daily requirements for certain nutrients, and starvation fails to provide them.

• Starvation decreases intestinal mass and surface area, which can interfere with nutrient absorption and increase the risk of bacterial translocation.

• Outcomes from starvation weight-loss programs versus restricted caloric intake programs reveal that the net weight loss with starvation is roughly equivalent to that with restricted caloric intake, but it comes at a much higher cost to the pet.

• Starvation is perceived as inhumane by most clients and veterinarians and destroys the client-veterinarian partnership needed for successful weight loss. If clients do not feel good about a dog's weight-loss program, they will probably refuse to participate or discontinue it prematurely.

• Both short- and long-term successes are important components of a weight-loss program. Starvation does not provide the owner with the tools to modify the pet's lifestyle.

Step 8—Divide total daily caloric intake into two meals. Meal size and frequency influence postprandial thermogenesis in dogs.39 Thermogenesis is increased by feeding multiple small meals rather than one large meal (i.e. it takes calories to digest food). Additionally, two smaller meals may provide better satiety than one large meal.

Step 9—Allow treats to be given, if this is part of the owner-animal bond. The human-animal bond is important to maintain during a weight-loss program, and treats play an important role in some of those relationships. If clients who are used to giving treats are told to discontinue treats "cold turkey," they may tell you that they have quit, but persist in giving treats on the side. It is better to provide the client with a list of alternatives they can use for treats. One important goal is to change the owner's habits that contributed to the pet's weight gain. Providing the client with a list of options for treats gets this process started.

Provide low-calorie treat options, and limit the amount of treats to less than 10% of the dog's total daily caloric intake.

Step 10—Decide on a rate of weight loss. Because dogs are not uniform in size, it is better to recommend a percentage of body weight to lose each week than a standard generic quantity for all dogs. A weight-loss rate of 1% of body weight per week is safe.

Step 11—Weigh the dog at least every two weeks. This frequency of monitoring allows early detection if weight loss is too slow or has plateaued. This frequency also prevents the owner from investing months of time and money into a program that is not working. Frequent weight checks also provide an opportunity to celebrate successes with the owner and to continue to motivate him or her to continue with the program.

Summary

Obesity is considered a chronic inflammatory disease, and many of the health risks associated with obesity can be attributed to this chronic inflammatory state. However, obesity is a treatable condition. Many of the health-associated abnormalities from obesity will resolve or improve with weight loss. Eppie's case (see sidebar "Eppie: Successful weight loss with a step-by-step approach") illustrates the importance of weight loss for improving Eppie's quality of life and enabling her to perform her function as a guide dog. Her forelimb lameness also resolved after the weight loss.

Eppie: Successful weight loss with a step-by-step approach

Sherry Sanderson, DVM, PhD, DACVIM, DACVN, Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

REFERENCES

1. Edney ATB, Smith PM. Study of obesity in dogs visiting veterinary practices in the United Kingdom. Vet Rec 1986;118:391-396.

2. McGreevy PD, Thomson PC, Pride C, et al. Prevalence of obesity in dogs examined by the Australian veterinary practices and the risk factors involved. Vet Rec 2005;156:695-702.

3. Laflamme DP. Understanding and managing obesity in dogs and cats. Vet Clin North Am Small Anim Pract 2006;36:1283-1295.

4. Zhang YY, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homolog. Nature 1994;372:425-432.

5. Trayhurn P, Bing C, Wood IS. Adipose tissue and adipokines — energy regulation from the human perspective. J Nutr 2006;136:1935S-1939S.

6. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295.

7. Ishioka K, Hosoya K, Kitagawa H, et al. Plasma leptin concentration in dogs: effects of body condition score, age, gender and breeds. Res Vet Sci 2007;82:11-15.

8. Jeusette IC, Detilleux J, Shibata H, et al. Effects of chronic obesity and weight loss on plasma ghrelin and leptin concentrations in dogs. Res Vet Sci 2005;79:169-175.

9. Scarpace PJ, Kumar MV, Bouchard GF, et al. Dietary vitamin A supplementation: role of obesity and leptin regulation in the dog and cat. In: Reinhart, GA, Carey DP, ed. Recent advances in canine and feline nutrition (2000 Iams Nutrition Symposium Proceedings). Vol 3, Wilmington, Ohio, 2000, Orange Frazer Press, pp 103-111.

10. Margetic S, Gazzola C, Pegg GG, et al. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002;26:1407-1433.

11. Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003;278:2461-2468.

12. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-946.

13. Yokota T, Oritani K, Takahasha I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000;96:1723-1732.

14. Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003;285:E527-E533.

15. Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752-1761.

16. Tsunoda M, Kobayashi N, Ide T, et al. A novel PPAPα agonist ameliorates insulin resistance in dogs fed a high-fat diet. Am J Physiol Endocrinol Metab 2008;294:E833-E840.

17. 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.

18. Varady KA, Tussing L, Bhutani S, et al. Degree of weight loss required to improve adipokine concentrations and decrease fat cell size in severely obese women. Metab Clin Exp 2009;58:1096-1101.

19. Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression of type 2 diabetes in rhesus monkeys. Diabetes 2001;50:1126-1133.

20. Hu E, Liang P, Spiegelman BM. Adipo is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697-10703.

21. Engstrom G, Hedblad B, Stavenow L, et al. Inflammation-sensitive plasma proteins are associated with future weight gain. Diabetes 2003;52:2097-2101.

22. Festa A, D'Agostino R Jr, Williams K, et al. The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obesity 2001;25:1407-1415.

23. Yudkin JS, Stehouwer CD, Emeis JJ, et al. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999;19:972-978.

24. Johnston SA. Osteoarthritis: joint anatomy, physiology and pathobiology. Vet Clin North Am Small Anim Pract 1997;27:699-723.

25. Grotle M, Hagen KB, Natvig B et al. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskeletal Disorders 2008;132: doi: 10.1186/1471-2474-9-132.

26. Dahaghin S, Bierma-Zeinstra SMA, Koes BW, et al. Do metabolic factors add to the effect of overweight on hand osteoarthritis? The Rotterdam Study. Ann Rheum Dis 2007;66:916-920.

27. Reijman M, Pols HAP, Bergink AP, et al. Body mass index associated with onset and progression of osteoarthritis of the knee but not the hip: The Rotterdam Study. Ann Rheum Dis 2007;66:158-162.

28. Gualillo O. Editorial. Further evidence for leptin involvement in cartilage homeostasis. Osteoarthritis Cartilage 2007;15:857-860.

29. Simopoulou T, Malizos KN, Iliopoulos D, et al. Differential expression of leptin and leptin's receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthritis Cartilage 2007;15:872-883.

30. Kealy RD, Lawler DF, Ballam JM, et al. Five-year longitudinal study on limited food consumption and development of osteoarthritis in coxofemoral joints of dogs. J Am Vet Med Assoc 1997;210: 222-225.

31. 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.

32. Runges JJ, Biery DN, Lawler DF, et al. The effects of lifetime food restriction on the development of ostseoarthritis in the canine shoulder. Vet Surg 2008;37:102-107.

33. Smith GK, Paster EF, Powers MY, et al. Lifelong diet restriction and radiographic evidence of osteoarthritis in the hip joint in dogs. J Am Vet Med Assoc 2006;229:690-693.

34. Christensen R, Bartels EM, Astrup A, et al. Effect of weight reduction in obese patients diagnosed with knee osteroarthritis: a systematic review and meta-analysis. Ann Rheum Dis 2007;66:433-439.

35. Burkholder WJ, Hulse DA. Weight loss to optimal body condition increases ground reactive forces in dogs with osteroarthritis. In Proceedings Purina Nutrition Forum 2000;74.

36. Impellizeri JA, Tetrick MA, Muir P. Effect of weight reduction on clinical signs of lameness in dogs with hip osteoarthritis. J Am Vet Med Assoc 2000;216:1089-1091.

37. Mlacnick E, Bockstahler BA, Muller M, et al. Effects of caloric restriction and a moderate or intense physiotherapy program for treatment of lameness in overweight dogs with osteoarthritis. J Am Vet Med Assoc 2006;229:175-1760.

38. Marshall WG, Hazewinkel HAW, Mullen D, et al. The effect of weight loss on lameness in obese dogs with osteroarthritis. Vet Res Commun 2010;34:241-253.

39. LeBlanc J, Diamond P. Effect of meal size and frequency on postprandial thermogenesis in dogs. Am J Physiol Endocrinol Metab 1986;250:E144-E147.