High-density lipoprotein remains elevated despite reductions in total cholesterol in fasting adult male elephant seals (Mirounga angustirostris)

Tift, Michael S.; Houser, Dorian S.; Crocker, Daniel E.

doi:10.1016/j.cbpb.2011.04.005

Cited by 19 publications

(15 citation statements)

References 56 publications

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“…Adaptations that potentially decrease such risks in marine mammals include hypoxic pulmonary vasodilatation and elevations in both antioxidant concentrations and antioxidant enzyme activities (Zenteno-Savín et al, 2002;Olson et al, 2010;Tift et al, 2011;Vázquez-Medina et al, 2011). We propose that the levels of heme degradation, and associated by-products such as endogenous CO found in elephant seals, may also contribute to the protection against these conditions.…”

Section: Potential Therapeutic Benefits Of Elevated Co In Marine Mammalsmentioning

confidence: 96%

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal

Tift

Ponganis

Crocker

2014

Journal of Experimental Biology

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Low concentrations of endogenous carbon monoxide (CO), generated primarily through degradation of heme from hemeproteins, have been shown to maintain physiological function of organs and to exert cytoprotective effects. However, high concentrations of carboxyhemoglobin (COHb), formed by CO binding to hemoglobin, potentially prevent adequate O 2 delivery to tissues by lowering arterial O 2 content. Elevated heme-protein concentrations, as found in marine mammals, are likely associated with greater heme degradation, more endogenous CO production and, consequently, elevated COHb concentrations. Therefore, we measured COHb in elephant seals, a species with large blood volumes and elevated hemoglobin and myoglobin concentrations. The levels of COHb were positively related to the total hemoglobin concentration. The maximum COHb value was 10.4% of total hemoglobin concentration. The mean (±s.e.m.) value in adult seals was 8.7±0.3% (N=6), while juveniles and pups (with lower heme-protein contents) had lower mean COHb values of 7.6±0.2% and 7.1±0.3%, respectively (N=9 and N=9, respectively). Serial samples over several hours revealed little to no fluctuation in COHb values. This consistent elevation in COHb suggests that the magnitude and/or rate of heme-protein turnover is much higher than in terrestrial mammals. The maximum COHb values from this study decrease total body O 2 stores by 7%, thereby reducing the calculated aerobic dive limit for this species. However, the constant presence of elevated CO in blood may also protect against potential ischemia-reperfusion injury associated with the extreme breath-holds of elephant seals. We suggest the elephant seal represents an ideal model for understanding the potential cytoprotective effects, mechanisms of action and evolutionary adaptation associated with chronically elevated concentrations of endogenously produced CO. KEY WORDS: Calculated aerobic dive limit, Carbon monoxide, Hemoglobin absorption spectra, Marine mammal, Oxygen stores INTRODUCTIONCarbon monoxide (CO) is often classified as a strictly toxic gas, depriving the body of oxygen (O 2 ) by binding to heme-proteins such as hemoglobin and forming carboxyhemoglobin (COHb) (Weaver, 2009). Deleterious symptoms (e.g. headache, nausea and shortness of breath) of CO-driven hypoxia are typically seen when COHb values reach ≥20% of total hemoglobin concentration, and death is associated with values of 50-80% (Stewart, 1975;Weaver, 2009 storage capacity (decreased arterial O 2 content), thus limiting mitochondrial respiration. However, CO is also generated endogenously in low concentrations, and functions in neurotransmission and in protection of tissues and cells against inflammation, apoptosis and ischemia-reperfusion injuries (Snyder et al., 1998; Kevin and Laffey, 2008;Mustafa et al., 2009; Kajimura et al., 2010;Prabhakar, 2012). Therefore, low concentrations of CO can provide beneficial and therapeutic effects up to a specific concentration, at which elevated CO then leads to detrimental effects from reduce...

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Section: Potential Therapeutic Benefits Of Elevated Co In Marine Mammalsmentioning

confidence: 96%

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal

Tift

Ponganis

Crocker

2014

Journal of Experimental Biology

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“…Second, the total lipid profile is markedly different within fasting adult males, which may or may not be reflected in the other age categories but which is certainly closer within the seals than in comparison to humans. Specifically, levels of total cholesterol and low density lipoprotein are elevated relative to humans but do decline with time fasting, from 10.2 to 6.9 mM and 4.2 to 2.0 mM, respectively (49). High-density lipoprotein is also high but is maintained across the breeding fast in males ranging from 4.6 to 5.7 mmol/L, well in excess of the threshold below which NCEP sets as one of the defining criteria of the metabolic syndrome (HDL ≤1.03 mM for males, ≤1.29 mM for females).…”

Section: Regulation Of Glucose Metabolismmentioning

confidence: 99%

A Non-Traditional Model of the Metabolic Syndrome: The Adaptive Significance of Insulin Resistance in Fasting-Adapted Seals

2013

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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.

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“…Increased activity and protein expression of several antioxidant enzymes (SOD, catalase, GPx, Prx, GST, GR, G6PDH, glutamate-cysteine ligase =GCL, -glutamyl-transpeptidase: GTT), as well as increased GSH, likely contribute to the prevention of fasting-associated oxidative damage in elephant seal pups (Vázquez-Medina et al 2011c; Vázquez-Medina et al 2010). Increased plasma content of water-soluble vitamins in pups and lactating females (Boaz et al 2012), and the maintenance of elevated levels of high-density lipoproteins in breeding and molting adult males (Tift et al 2011), may also contribute to counteract fasting-induced oxidant production in elephant seals. The understanding of how the antioxidant system of the northern elephant seal is up-regulated in response to prolonged fasting remains elusive, but preliminary studies from our laboratories, along with the present findings, suggest that angiotensin II stimulates Nox4 by increasing transforming growth factor (TGF and that Nox4 may mediate an hormetic response by activating Nrf2 (Figure 2).…”

Section: In Vivo Studiesmentioning

confidence: 99%

Coping with physiological oxidative stress: a review of antioxidant strategies in seals

et al. 2012

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While diving, seals are exposed to apnea-induced hypoxemia and repetitive cycles of ischemia/reperfusion. While on land, seals experience sleep apnea, as well as prolonged periods of food and water deprivation. Prolonged fasting, sleep apnea, hypoxemia and ischemia/reperfusion increase oxidant production and oxidative stress in terrestrial mammals. In seals, however, neither prolonged fasting nor apnea-induced hypoxemia or ischemia/reperfusion increase systemic or local oxidative damage. The strategies seals evolved to cope with increased oxidant production are reviewed in the present manuscript. Among these strategies, high antioxidant capacity and the oxidant-mediated activation of hormetic responses against hypoxia and oxidative stress are discussed. In addition to expanding our knowledge of the evolution of antioxidant defenses and adaptive responses to oxidative stress, understanding the mechanisms that allow adapted mammals to avoid oxidative damage has the potential to advance our knowledge of oxidative stress-induced pathologies and to enhance the translative value of biomedical therapies in the long term.

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High-density lipoprotein remains elevated despite reductions in total cholesterol in fasting adult male elephant seals (Mirounga angustirostris)

Cited by 19 publications

References 56 publications

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal

A Non-Traditional Model of the Metabolic Syndrome: The Adaptive Significance of Insulin Resistance in Fasting-Adapted Seals

Coping with physiological oxidative stress: a review of antioxidant strategies in seals

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