Improvement in insulin resistance and reduction in plasma inflammatory adipokines after weight loss in obese dogs
Introduction
Obesity is defined as a disease in which excess body fat has accumulated such that health may be adversely affected [1]. Obese humans are known to suffer from several associated clinical conditions including hypertension, coronary heart disease, certain cancers (eg, breast, ovarian, prostate), osteoarthritis, respiratory disease, and reproductive disorders [1]. Similarly, obesity has detrimental effects on the health of dogs, with disease associations including orthopedic diseases, respiratory disease, urinary tract disorders, and decreased longevity [2], [3], [4]. However, a possible association between obesity and cancer is controversial is dogs, with one study suggesting an association [2], whilst another suggested no relationship [5].
In humans, the most important disease association is that of the metabolic syndrome, a group of metabolic and vascular disorders, which increase the risk of an individual developing type 2 diabetes and cardiovascular disease [6]. The risk of developing diabetes increases with increasing body mass index (BMI); individuals with a BMI > 30 kg/m2 are 10 times more likely to develop type 2 diabetes than those with a BMI < 25 kg/m2 [7]. In contrast, dogs more commonly suffer from a form of diabetes resembling type 1 diabetes in man [8], [9], [10], and although common, its pathogenesis is poorly understood [11], [12], [13]. Although dogs do not commonly suffer from type 2 diabetes [11], [12], [13], a previous study has reported an association between canine diabetes and excess body weight [2]. The reason for such an association is not clear but may be owing to insulin resistance, which can be induced experimentally in dogs through dietary manipulation [14], [15], [16], [17]. Further, lifelong dietary energy restriction has been shown to improve insulin sensitivity and glucose tolerance [18], and a relationship between obesity, glucose tolerance, and insulin response was reported in one study of dogs with naturally occurring diabetes [19]. However, in that study, the degree of excess weight was estimated subjectively using breed standards, which is a notoriously unreliable method for quantifying adiposity. Therefore, further studies are clearly required to clarify the link between insulin resistance in naturally occurring canine obesity.
White adipose tissue (WAT) has recently been recognized as an active endocrine organ that is capable of secreting a wide range of hormones and protein factors, collectively termed adipokines [20], [21]. Of particular note is the range of cytokines, chemokines, and other inflammation-related proteins secreted by WAT, such that a state of chronic low-grade systemic inflammation is now known to exist in obesity [22], [23]. Systemic concentrations of acute-phase proteins (eg, C-reactive protein [CRP], haptoglobin) and pro-inflammatory cytokines (eg, IL-6 and tumor necrosis factor-α [TNFα]) are elevated in obese individuals [24]. Since adipose tissue is an important source of these factors [23], this organ system may contribute significantly to the elevated circulating concentrations [23], providing a link between obesity, insulin resistance, and the metabolic syndrome in humans [25], [26]. Further, weight loss in these subjects has been shown to reverse this low-grade inflammatory state and to improve insulin sensitivity [27].
Our recent work has demonstrated that genes encoding key inflammatory adipokines are expressed in canine WAT samples and in canine adipocytes differentiated in culture [28], [29]. However, studies examining adipokine profiles in canine obesity and associated disease, including insulin resistance, are limited. Therefore, the purpose of the current study was to assess insulin sensitivity and inflammatory adipokine profiles in dogs with naturally occurring obesity and to determine the effect of subsequent weight loss.
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Study animals
Twenty-six dogs were included in this study; all were referred to the Royal Canin Weight Management Clinic (RCMWC), University of Liverpool, United Kingdom (UK), for the investigation and management of obesity or obesity-related disorders. Dogs were enrolled if they were systemically well, euthyroid, and had no significant abnormalities on complete blood count, serum biochemical analysis, and urinalysis. The study was performed in adherence to the University of Liverpool Animal Ethics
Baseline characteristics of the diet groups
Of the 26 dogs in the study, breeds represented included crossbred (7), Labrador retriever (6), Cavalier King Charles spaniel (4), Yorkshire terrier (4), golden retriever (2), border collie (1), cocker spaniel (1), and German shepherd dog (1). The median (range) age was 83 mo (19-166 mo). Fifteen dogs were male (11 neutered), whereas all of the 11 female dogs were neutered. Full details of the outcome of the weight loss program are given in Table 2. The mean (± SD) percentage of weight lost was
Discussion
The current study has demonstrated the presence of insulin resistance, as judged by elevated fasting plasma insulin concentration and I:G ratio, in obese dogs prior to weight loss. Nonetheless, although glucose concentrations were marginally elevated in 4 of 26 dogs, the degree of elevation was of doubtful clinical significance. However, both insulin concentrations and I:G ratio decreased significantly, suggesting improved insulin sensitivity, when dogs lost weight using a conventional regimen
Conflict of interest statement
The following conflicts of interest apply: A.J.G.’s senior lectureship is funded by Royal Canin; the diet used in this study is manufactured by Royal Canin; P.J.M. is an employee of WALTHAM; and V.B. is employed by Royal Canin.
Acknowledgments
The authors wish to acknowledge the referring veterinarians for referring cases, the owners of all dogs for allowing them to participate, and the clinical staff at the University of Liverpool for assistance with case management. Renaud Sergheraert and John Rawlings are acknowledged for their assistance. The contribution made by each author is as follows: A.J.G: designed study, collected clinical data, analyzed results, drafted paper; S.L.H: collected clinical data, reviewed manuscript; M.H.:
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