Managing weight loss in dogs and cats (Proceedings)

Prevention of Obesity in Dogs And Cats

The number of pets that are overweight or obese has reached epidemic proportions in the USA and other industrialized countries. For example, just over 35% of adult cats in the USA are overweight or obese. As veterinarians, we need to be proactive on focusing on obesity prevention. Wellness visits are the ideal time to regularly re-assess body weight history and body condition score. The benefits of maintaining a pet in lean body condition, and the health risks (and expense) that can accompany obesity are important owner education topics. The veterinary visit for spaying/neutering is an important, but often neglected, opportunity to reassess diet type and feeding management and make appropriate awareness of obesity issues to clients. Studies in cats have shown that neutering decreases metabolic rate by 25-33%. Neutered animals, however, usually have increased fat mass. When energy expenditure is expressed on a lean mass basis, no difference in metabolic rate is noted between neutered and entire individuals. Alternative explanations for the effect of neutering on obesity is an alteration in feeding behavior leading to increased food intake and decreased activity, without a corresponding decrease in energy intake.

Middle-aged neutered male cats and middle-aged spayed female dogs are at highest risk of becoming obese. Some purebred dogs are at higher risk of becoming obese'; these include Shetland Sheepdogs, Golden Retrievers, Dachshunds, Cocker Spaniels, Labrador Retrievers, Dalmatians, and Rottweilers. Manx cats are more likely to become obese than other purebred cats. Not surprisingly, low activity level increases risk for weight gain in both species; in cats, apartment dwelling is associated with a higher risk. Obesity in dogs is associated with the number of meals and snacks fed, the feeding of table scraps, and the dog's presence when its owners prepared or ate their own meal.

Weight Management

The first step in managing obesity is getting owners to recognize it as a problem. A weight reduction protocol must be tailored for the individual patient, with consideration given to the following components: initial assessment of health status and any disease conditions present concurrently with obesity, caloric intake, diet selection, exercise, behavioral modification, pharmacologic intervention, follow up, and weight maintenance after optimal weight is achieved. A successful weight loss program requires some combination of reduction in caloric intake (owner compliance) and an increase in physical activity. A pharmacologic aid to decrease caloric intake can also be considered as part of the program for dogs.

Diet

Results from the emerging field of nutragenomics show differences in gene expression profiles in lean and obese pets. Nutragenomics has been used to develop diets that alter gene expression in obese pets to more closely resemble the gene expression profiles in lean pets. Furthermore, preliminary data suggest that weight loss can correct the systemic effects of obesity. Microarray analysis indicates that the gene expression of adipocytes and lymphocytes from obese dogs and cats, compared to lean pets, show a down regulation of genes such as PPAR-gamma, uncoupling protein-2, carnitine O-palmitoyltransferase 1 A and acyl-CoA synthetase that are important in the beta-oxidation of fatty acids (Yamka, R.M., K.G. Friesen, et al. The effects of weight loss on gene expression in dogs. 2008 ACVIM Meeting, San Antonio). Down-regulation of these genes may explain why obese animals are fat-storing instead of fat-burning. In addition, adipose tissue from obese pets shows down-regulation of genes associated with glucose metabolism, such as pyruvate dehydrogenase kinase-4 and glucose-6-phosphatase. These observations may explain why obese animals become insulin resistant and have increased circulating glucose, insulin, IGF-1 and inflammation.

Although energy restriction can be achieved by feeding the pet's regular food, this approach has the disadvantage of causing excessive loss of lean body mass as well as having the potential to deplete essential micronutrients. Therefore, it is strongly recommended to use purpose-formulated weight loss diets, which generally are restricted in fat and energy, but are higher than adult maintenance diets in protein and micronutrients. Enhanced amounts of protein are very important because the amount of lean tissue lost is minimized even though the weight loss is not more rapid.

Additional dietary factors that may be of benefit for weight loss include L-carnitine supplementation, high-fiber diets, and conjugated linoleic acid (CLA). L-Carnitine is an amino acid that is synthesized de novo in the liver and kidneys from lysine and methionine in the presence of ascorbate. Dietary supplementation of L-carnitine improves nitrogen retention, increasing lean mass and reducing fat mass. Incorporation of L-carnitine at a level of 50–300 ppm in weight reduction diets has been shown to reduce lean tissue loss during weight loss. Possible mechanisms for this protective effect on lean tissue include enhancing fatty acid oxidation and energy availability for protein synthesis during times of need. There is also controversy concerning the effect of fiber satiety; some reports suggested that feeding up to 12–16% of dry matter as dietary fiber has no effect, whereas other work demonstrated appetite suppression when 21% of the diet was consumed as diet ary fiber. Data is conflicting on the possible benefit of CLA in weight loss diets. Studies in experimental animals suggested that it has an antiadipogenic effect, but data on the use of CLA as an antiobesity agent in humans and cats are conflicting, with the most recent data suggesting lack of a significant effect.

Exercise

Increasing physical activity is a useful adjunct to dietary therapy. When used in combination with dietary therapy, it promotes fat loss and may assist in lean tissue preservation. There is also some human evidence that exercise may help prevent the rapid regain in weight that can occur after successful weight loss. The exact program must be tailored to the individual and take into account any concurrent medical concerns. Suitable exercise strategies in dogs include walking, swimming, hydrotherapy, and treadmill exercise. Exercise in cats can be encouraged by increasing play activity, using cat toys or motorized units. Cats can also be encouraged to "work" for their food by using feeding toys or moving the food bowl between rooms before feeding.

Pharmacology

Dirlotapide (Slentrol) is a relatively new drug approved for management of canine obesity. It is in a class of drugs that inhibit microsomal triglyceride transfer protein (MTP). MTP is involved in secreting VLDL (lipoproteins made of apo-lipoprotein B- apoB) into the blood stream from the liver, and chylomicrons from the intestine. The assembly of apoB-containing lipoproteins (VLDL and subsequently LDL) requires MTP, which shuttles triglycerides onto the nascent lipoprotein. The assembly and secretion of chylomicrons by intestines is dependent on MTPs. Inhibition of MTP delays absorption of fats from the intestine. Preferential inhibition of intestinal MTPs rather than hepatic MTPs makes this drug useful in dogs but not other species, including people and cats. Note that dirlotapide is contraindicated in cats because of concerns about hepatic lipidosis from marked reduction in appetite and/or accumulation of lipids in the liver due to altered metabolism.

The mechanism by which dirlotapide produces weight loss is primarily from the accumulation of triglycerides in enterocytes, which results in secretion of satiety hormones such as PYY and GLP-1, leading to a voluntary decrease in caloric intake. A minor contribution to weight loss comes from reduced fat absorption.

All dogs being considered for dirlotapide therapy should undergo a thorough history and physical examination that includes laboratory tests to screen for underlying conditions. Pre-existing endocrine disease, including hyperadrenalcorticalism (Cushing's disease), should be managed prior to use of dirlotapide. Up to 25% of dogs experience vomiting episodes during therapy, but the vomiting is usually transient and mild/temporary (most often a single event), usually during upward titration of the dose and dogs do not appear to feel ill. Dirlotapide may produce a mild to moderate elevation in serum hepatic transaminase activity. If the elevation in alanine aminotransferase (ALT) activity is mild, the drug can be continued, with monitoring as needed. If there is a marked elevation in ALT activity or there is a simultaneous increase in aspartate aminotransferase (AST), alkaline phosphatase (ALP), á-glutamyl transferase (GGT), or total bilirubin, treatment should be discontinued. Increases in hepatic transaminase activity usually decrease when dirlotapide is discontinued. Other less frequent side effects are loose stools, diarrhea, lethargy and loss of appetite.

The success rate of traditional diet and exercise weight loss programs in dogs has been reported to be as low as 8%. The ability to take control of appetite is a novel approach to weight management that will enhance client compliance and success in some cases. It can be particularly useful when a concurrent condition, such as ruptured cruciate ligament, makes weight loss particularly important but very difficult. Even with pharmacologic assistance, dogs have varied responses (i.e. some dogs lose weight quickly and have very little appetite, other dogs maintain their appetite right through the entire treatment, but still lose a little weight, and there is that occasional dog that will even gain a little weight). Let owners know that a plateau will be reached at some point and that plateau may last for several months. During weight loss using dirlotapide, do not have the owners feed a low calorie food, as the drug works best with a higher fat intake (Purina JM is a good choice). As ideal weight is approached, the dog must be transitioned to a reduced-fat diet suitable for weight maintenance in order to avoid weight rebound after the drug is discontinued and the dog's usual appetite is regained.

Follow Up

A recent study demonstrated that weight loss is more successful if an organized strategy is followed with regular weigh-in sessions. When using dirlotapide,it is helpful to put one person in the practice in charge of calling the owners back and scheduling one month weigh-ins so that they become familiar with common questions asked. The computer program provided by Pfizer for dosing dirlotapide correctly is very helpful, and the accompanying weight charting tool is an ideal aid to get clients back for monthly rechecks.

It is essential to continue to monitor body weight after ideal weight has been achieved to ensure that weight that was lost is not regained. As with humans, a rebound effect has been demonstrated after weight loss in dogs and cats. It has been shown that energy restriction results in a mass-adjusted decrease in energy expenditure in cats that is maintained after weight regain. Such metabolic adaptations mean that weight management will be a long term challenge in most patients even after a successful weight loss program.

Selected Readings

Laflamme DP. Understanding and managing obesity in dogs and cats. Vet Clin Small An Pract 2006; 36; 1283-95, vii.

German AJ. The growing problem of obesity in dogs and cats. J Nutr 2006; 136:1940S-1946S.