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A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

Houser DS, Champagne CD, Crocker DE - Front Endocrinol (Lausanne) (2013)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Conservation and Biological Research, National Marine Mammal Foundation , San Diego, CA , USA.

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.

No MeSH data available.


Related in: MedlinePlus

Variations in metabolic pathways with time fasting that contribute to insulin resistance in the northern elephant seals. The model draws upon findings from multiple age classes and likely demonstrates age and gender-specific variations. Dashed lines indicate reductions in metabolite or hormone production, bold lines indicate increased production, and normally weighted lines indicate no change. Arrows next to a metabolite or hormone indicate either increased levels (upward arrow) or decreased levels (downward arrow). (EGP, endogenous glucose production; NEFA, non-esterified fatty acids; TNF-α, tumor necrosis factor alpha; IRS-1, phosphorylated form of insulin receptor substrate; IR, phosphorylated form of insulin receptor; Akt2, expression of the Akt2 gene; Glut-4, expression of the plasma membrane glucose transporter 4.)
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Figure 2: Variations in metabolic pathways with time fasting that contribute to insulin resistance in the northern elephant seals. The model draws upon findings from multiple age classes and likely demonstrates age and gender-specific variations. Dashed lines indicate reductions in metabolite or hormone production, bold lines indicate increased production, and normally weighted lines indicate no change. Arrows next to a metabolite or hormone indicate either increased levels (upward arrow) or decreased levels (downward arrow). (EGP, endogenous glucose production; NEFA, non-esterified fatty acids; TNF-α, tumor necrosis factor alpha; IRS-1, phosphorylated form of insulin receptor substrate; IR, phosphorylated form of insulin receptor; Akt2, expression of the Akt2 gene; Glut-4, expression of the plasma membrane glucose transporter 4.)

Mentions: Figure 2 provides a summary of changes in metabolic pathways that occur with the progression of fasting in elephant seals. The diagram is somewhat hypothetical in that it combines findings from different age classes of seal, but it also demonstrates adaptive variations that may be shared with other marine mammals. A common factor among all cetacean and pinniped species is that they have evolved a secondary aquatic existence over tens of millions of years while capitalizing on a diet that is high in lipid and protein content but essentially devoid of carbohydrate. The result of this dietary pressure may very well have produced a convergence of metabolic adaptations that parallel those of pathological states in terrestrial mammals, particularly in humans where an overabundance of energy rich foods taxes a system originally designed for dealing with food shortages. The metabolic characteristics of prolonged fasting in the elephant seal described here are not unique to this species. Evidence obtained from other marine mammals, including odontocete cetaceans (e.g., toothed whales such as dolphins) and both otariid and phocid seals (i.e., sea lions and fur seals, and true seals, respectively), suggests that the same traits are expressed to some degree within many species of these divergent, phylogenetic lineages. For example, high fasting blood glucose is observed in a number of pinnipeds with widely varying fasting durations (69–72) and is even observed in dolphins fasting for periods of several days (73). Other physiological parallels to the metabolic syndrome and diabetes mellitus have also been noted (74); however, the degree to which there are parallels varies according to the physiological ecology of the species. For example, pups of both the subantarctic fur seal (Arctocephalus tropicalis) and the northern elephant seal undergo extreme fasts of up to 3 months, but the hormonal regulation of substrate utilization during the fasts is markedly different, likely because of the more restricted nutrient reserves in the smaller subantarctic fur seal (75).


A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

Houser DS, Champagne CD, Crocker DE - Front Endocrinol (Lausanne) (2013)

Variations in metabolic pathways with time fasting that contribute to insulin resistance in the northern elephant seals. The model draws upon findings from multiple age classes and likely demonstrates age and gender-specific variations. Dashed lines indicate reductions in metabolite or hormone production, bold lines indicate increased production, and normally weighted lines indicate no change. Arrows next to a metabolite or hormone indicate either increased levels (upward arrow) or decreased levels (downward arrow). (EGP, endogenous glucose production; NEFA, non-esterified fatty acids; TNF-α, tumor necrosis factor alpha; IRS-1, phosphorylated form of insulin receptor substrate; IR, phosphorylated form of insulin receptor; Akt2, expression of the Akt2 gene; Glut-4, expression of the plasma membrane glucose transporter 4.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814516&req=5

Figure 2: Variations in metabolic pathways with time fasting that contribute to insulin resistance in the northern elephant seals. The model draws upon findings from multiple age classes and likely demonstrates age and gender-specific variations. Dashed lines indicate reductions in metabolite or hormone production, bold lines indicate increased production, and normally weighted lines indicate no change. Arrows next to a metabolite or hormone indicate either increased levels (upward arrow) or decreased levels (downward arrow). (EGP, endogenous glucose production; NEFA, non-esterified fatty acids; TNF-α, tumor necrosis factor alpha; IRS-1, phosphorylated form of insulin receptor substrate; IR, phosphorylated form of insulin receptor; Akt2, expression of the Akt2 gene; Glut-4, expression of the plasma membrane glucose transporter 4.)
Mentions: Figure 2 provides a summary of changes in metabolic pathways that occur with the progression of fasting in elephant seals. The diagram is somewhat hypothetical in that it combines findings from different age classes of seal, but it also demonstrates adaptive variations that may be shared with other marine mammals. A common factor among all cetacean and pinniped species is that they have evolved a secondary aquatic existence over tens of millions of years while capitalizing on a diet that is high in lipid and protein content but essentially devoid of carbohydrate. The result of this dietary pressure may very well have produced a convergence of metabolic adaptations that parallel those of pathological states in terrestrial mammals, particularly in humans where an overabundance of energy rich foods taxes a system originally designed for dealing with food shortages. The metabolic characteristics of prolonged fasting in the elephant seal described here are not unique to this species. Evidence obtained from other marine mammals, including odontocete cetaceans (e.g., toothed whales such as dolphins) and both otariid and phocid seals (i.e., sea lions and fur seals, and true seals, respectively), suggests that the same traits are expressed to some degree within many species of these divergent, phylogenetic lineages. For example, high fasting blood glucose is observed in a number of pinnipeds with widely varying fasting durations (69–72) and is even observed in dolphins fasting for periods of several days (73). Other physiological parallels to the metabolic syndrome and diabetes mellitus have also been noted (74); however, the degree to which there are parallels varies according to the physiological ecology of the species. For example, pups of both the subantarctic fur seal (Arctocephalus tropicalis) and the northern elephant seal undergo extreme fasts of up to 3 months, but the hormonal regulation of substrate utilization during the fasts is markedly different, likely because of the more restricted nutrient reserves in the smaller subantarctic fur seal (75).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Conservation and Biological Research, National Marine Mammal Foundation , San Diego, CA , USA.

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.

No MeSH data available.


Related in: MedlinePlus