IN-DEPTH: GERIATRIC MEDICINE/METABOLICS


loss in PL animals may have confounded this assess- ment, although it is noteworthy that within the PL cohort metabolic variables (insulin, triglycerides, etc) did not differ between obese (BCS 7) and non- obese (BCS 7) animals, suggesting that the meta- bolic derangement persists even after weight loss. Within the NL cohort, however, serum triglycerides, fasting insulin, and post-OST insulin were higher in obese when compared with nonobese animals. One interpretation of these findings is that obesity per se is not a requisite feature of the laminitis-prone (ie, EMS) phenotype, but components of the phenotype such as IR may be exacerbated when affected ani- mals become obese.38 This interpretation is consis- tent with anecdotal clinical observations of the laminitis-prone phenotype—not all affected animals express obesity or regional adiposity, whereas, con- versely, not all obese animals appear to be at in- creased risk of laminitis. Simply put, obesity in and of itself does not equate with EMS. In humans, too, it is now recognized that the pres-


ence of obesity-related metabolic disturbances, in- cluding IR, hyperlipidemia, inflammation, and hypertension, varies widely among obese individu- als.39,40 In fact, in some studies, up to 30% to 35% of obese adult humans have a metabolically healthy phenotype, giving rise to the term “metabolically healthy obese.”39 On the other hand, up to 40% of adults of normal weight and body mass index have metabolic perturbations typically associated with obesity and MetS, such as dyslipidemia, hyperinsu- linemia, and nonalcoholic fatty liver disease.39,40 Although the mechanisms underlying these differ- ent phenotypes are not fully understood, it is cur- rently believed that differences in visceral fat accumulation and the response of adipocytes to in- creased lipid accumulation are important factors.39 Adipose tissue produces a large array of proteins, including pro-inflammatory cytokines and other hormone-like proteins termed adipokines that exert local (paracrine) and systemic (endocrine) effects.41 Studies in animal models have indicated that obe- sity results in a progressive dysregulation of adipose tissue function, including marked pro-inflammatory signaling that leads to the development of a sys- temic inflammatory response, which, in turn, results in the development of IR and other metabolic abnor- malities.41,42 However, not all excess fat carries equal risk with visceral adiposity most strongly as- sociated with systemic inflammation and IR, per- haps because of higher cytokine and adipokine production as well as release of NEFAs into the portal circulation that contribute to the develop- ment of hepatic IR.42 Our preliminary observations that obesity per se


is not a defining feature of EMS mirrors findings in humans—IR and hypertriglyceridemia can occur in nonobese horses, whereas, conversely, the metabolic profile of some obese horses does not differ from that in lean individuals. One hypothesis is that obesity is not a primary cause of EMS but instead it may be


a marker of an underlying metabolic dysfunction, which, depending on other environmental factors (eg, diet, level of physical activity), drives adipose tissue accretion and development of obesity. If so, there are two very important implications for the identification and management of EMS. First, the presence or absence of obesity cannot be used as a diagnostic criterion. Second, whereas dietary re- striction and weight loss may result in some im- provement in insulin sensitivity and so forth in affected animals, the underlying metabolic dysfunc- tion is likely to persist. Thus, a diagnosis of EMS may be justified in some horses and ponies with recurrent laminitis problems that are not obese (or show regional adiposity) because they have other components of the phenotype, for example, hyper- insulinemia or high serum triglycerides. Then again, a diagnosis of EMS is not appropriate in horses or ponies that are obese (BCS 7) but with- out evidence of laminitis or disturbances in insulin dynamics and lipid metabolism. Further studies are needed to examine the impact


of obesity on the metabolic health of horses and its role in EMS. Cross-sectional studies have shown an inverse relationship between BCS and insulin sensitivity43 as well as positive relationships be- tween apparent adiposity, resting insulin concentra- tions, and blood markers of inflammation (eg, serum amyloid A, tumor necrosis factor (TNF)-, mRNA encoding for interleukin (IL)-1, and TNF-.43,44 On the other hand, adipose tissue (nuchal crest fat) and systemic markers of inflammation were un- changed in Arabian geldings after a 20% weight gain (increase in mean BCS [Henneke scale] from 6/9 to 8/9).a


Additionally, insulin sensitivity was un-


changed in Thoroughbred geldings after an 15% increase in body weight,45 whereas another recent study of horses and ponies reported no change in insulin sensitivity after an 20% in increase in fat mass.46 These observations reinforce the idea that factors other than BCS and adipose tissue mass contribute to variance in insulin sensitivity. Research is also needed to examine the role of


the adipokines leptin and adiponectin in EMS. Leptin, the product of the ob gene, provides infor- mation to the brain regarding the availability of body fat stores, promoting satiety and a reduction in food intake when energy balance is positive or fat stores are plentiful.47 Circulating leptin concen- trations are generally in direct proportion to body adipose mass.41,47 In contrast, serum adiponectin concentrations generally correlate inversely with fat mass, although in humans, hyperinsulinemia is associated with hypoadiponectinemia independent of fat mass.41 It has been proposed that high leptin and low adiponectin concentrations are useful markers of IR and EMS.22 Certainly, high leptin concentrations have been observed in insulin- resistant horses and ponies,7,8 including nonobese animals. In our own studies, however, serum lep- tin was not useful for the identification of laminitis-


AAEP PROCEEDINGS  Vol. 59  2013 301


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