Abstract
Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7–3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.
Highlights
Dyslipidemia, altered glucose metabolism, and hypertension are all hallmark characteristics of the metabolic syndrome that are often, but not always, associated with obesity
A decline in Endogenous glucose production (EGP) with time fasting is consistent with the fasting-associated down-regulation of glucose metabolism; the rate of glucose production in elephant seals fasting for 1–3 months is comparable to that of post-absorptive animals when controlling for mass [24]
SUMMARY The physiological response to fasting shared by mammals produces a state of insulin resistance that helps to conserve endogenous protein stores from net loss via gluconeogenesis and glucose oxidation and facilitates lipolysis in order to increase the reliance upon fat oxidation to meet the organism’s metabolic demands
Summary
Dyslipidemia, altered glucose metabolism, and hypertension are all hallmark characteristics of the metabolic syndrome that are often, but not always, associated with obesity. A brief description of the different classes of seal is given This is followed by a discussion of what is known about glucose metabolism and insulin resistance in this species, characteristics that make the elephant seal an atypical but potentially useful model of the metabolic syndrome. Elephant seals return to land either in the spring (females) or summer (males) to molt, following the post-breeding period return to sea to feed. During this “catastrophic” molt the entire pelage is shed and replaced. The highest glucose levels, which typically exceed 8 mM, are observed in elephant seals at the beginning of their post-weaning fast In this age class, there is a modest decrease in plasma glucose with the progression of the fast. ADULT FEMALE Early lactation 7.0 (0.7) Early lactation 7.4 (0.5) Early lactation 7.0 (0.2) Early lactation 7.6 (0.5)
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