The Veterinary Journal 213 (2016) 90
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The Veterinary Journal
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t v j l
Guest Editorial
Insulin dysregulation and obesity: You are what you eat
As endocrinopathic laminitis continues to enthral the veteri-
nary profession and horse owners alike, our understanding of the
conditions characterised by insulin dysregulation and consequent
laminitis evolves and advances. Since the original description of
equine metabolic syndrome (EMS) by Johnson (2002) and the
American College of Veterinary Internal Medicine (ACVIM) con-
sensus statement by Frank et al. (2010), matters have progressed,
with pathophysiological roles being postulated for incretins, in-
flammatory cytokines, insulin-like growth factor-1 receptors and
adipokines.
Some of these factors, along with the fundamental causal asso-
ciation between obesity and insulin dysregulation, are scrutinised
in the study by Dr Nicholas Bamford and colleagues, of the Univer-
sity of Melbourne, Australia, published in a recent issue of The
Veterinary Journal (Bamford et al., 2016). The most striking finding
in this study is that increased adiposity as a result of a hypercaloric,
high-fat ration was not associated with insulin dysregulation, in con-
trast to the effect of weight gain with a high-starch diet. As discussed
by the authors, this bears practical relevance to ration formula-
tion in insulin dysregulated horses that need to gain weight, for
example with pituitary pars intermedia dysfunction. Another in-
teresting aspect of these findings is the impact on the consideration
of what obesity actually is and how we assess it.
Obesity is defined as ‘abnormal or excessive fat accumulation that
presents a risk to health’1. It is well recognised both in humans and
in horses that there is more to obesity than simply the quantity of
adipose tissue; obesity is a functional and pathophysiological term
rather than simply a quantitative and morphological term. In order
to strictly establish the presence of obesity, it needs to be shown
that the adipose deposits within the animal are harmful and not
just simply above a threshold measure of mass. Conversely, to de-
scribe a laminitis-prone horse as ‘non-obese’ is a bold statement
without examination of the potential functionality of the individ-
ual’s fat deposits, irrespective of how little fat they appear to carry.
Regionally weighted measures of adiposity (Henneke et al., 1983)
or more focussed indices of regional adiposity, such as the ‘cresty’
neck score (Carter et al., 2009), perhaps implicitly acknowledge that
not all fat is the same, but nevertheless lack direct evidence of
adverse consequences of the fat deposits measured.
The study by Bamford et al. (2016) is a prime example of how
adiposity and obesity are not synonymous. In that study, doubling
the body fat mass of horses and ponies by feeding high fat or high
starch diets produced significantly different metabolic effects. Only
1 See: http://www.who.int/topics/obesity/en/
http://dx.doi.org/10.1016/j.tvjl.2016.03.010
1090-0233/© 2016 Elsevier Ltd. All rights reserved.
the high starch diet was associated with supposedly harmful con-
sequences, namely acquired insulin dysregulation, a decrease in the
beneficial adipokine high molecular weight (HMW) adiponectin and
a measurable increase in serum amyloid A, a systemic biomarker
of inflammation. Interestingly, another adipokine, leptin, did not
differ significantly between the two groups, supporting previous sug-
gestions that leptin simply reflects adiposity in a quantitative rather
than a qualitative manner.
Adiponectin is a 244 amino acid protein produced almost ex-
clusively by adipocytes and is structurally similar to tumour necrosis
factor α and related inflammatory proteins. In the circulation,
adiponectin tends to form trimers, hexamers or HMW multimers
consisting of four to six trimers. The HMW forms of adiponectin
appear to be the most biologically active, having anti-inflammatory
effects and increasing insulin sensitivity; these may be decreased
in obese horses (Bamford et al., 2016). HMW adiponectin may be
a key factor associating obesity with insulin dysregulation and is
emerging as a diagnostic target of potential interest for the assess-
ment and monitoring of clinical EMS. HMW adiponectin is
diagnostically attractive in that it appears to be largely unaffected
by diet, sex or age, has no discernible circadian rhythm and appears
to be reasonably stable in vitro.
Future studies will no doubt shed light on the diagnostic use-
fulness of HMW adiponectin and its association with insulin
dysregulation and a clinical endpoint, such as laminitis. Whatever
the outcome of such studies may be, there are clearly good clini-
cal and pathophysiological reasons to consider assessing adiposity
in more than simple morphological terms.
Andy E. Durham
Liphook Equine Hospital,
Liphook, Hampshire GU30 7JG, UK
E-mail address: andy.durham@theleh.co.uk
References
Bamford, N., Potter, S., Baskerville, C., Harris, P., Bailey, S.R., 2016. Effect of increased
adiposity on insulin sensitivity and adipokines concentrations in different equine
breeds adapted to cereal-rich or fat-rich meals. The Veterinary Journal.
Carter, R.A., Geor, R.J., Staniar, W.B., Cubitt, T.A., Harris, P.A., 2009. Apparent adiposity
assessed by standardised scoring systems and morphometric measurements in
horses and ponies. The Veterinary Journal 179, 204–210.
Frank, N., Geor, R.J., Bailey, S.R., Durham, A.E., Johnson, P.J., 2010. Equine metabolic
syndrome. Journal of Veterinary Internal Medicine 24, 467–475.
Henneke, D.R., Potter, G.D., Kreider, J.L., Yeates, B.F., 1983. Relationship between
condition score, physical measurements and body-fat percentage in mares. Equine
Veterinary Journal 15, 371–372.
Johnson, P.J., 2002. The equine metabolic syndrome: Peripheral Cushing’s syndrome.
Veterinary Clinics of North America. Equine Practice 18, 271–293.