scholarly journals Prolonged Fasting Induces Insulin Resistance in the Northern Elephant Seal Pup

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Jose A Viscarra ◽  
Daniel E Crocker ◽  
Rudy M Ortiz
Gene ◽  
2013 ◽  
Vol 526 (2) ◽  
pp. 155-163 ◽  
Author(s):  
José G. Soñanez-Organis ◽  
José P. Vázquez-Medina ◽  
Daniel E. Crocker ◽  
Rudy M. Ortiz

Author(s):  
Dana N. Wright ◽  
Kondwani G.H. Katundu ◽  
Jose A. Viscarra ◽  
Daniel E. Crocker ◽  
John W. Newman ◽  
...  

The prolonged, post-weaning fast of northern elephant seal (Mirounga angustirostris) pups is characterized by a reliance on lipid metabolism and reversible, fasting-induced insulin resistance providing a unique model to examine the effects of insulin on lipid metabolism. We have previously shown that acute insulin infusion induced a shift in fatty acid metabolism dependent on fasting duration. This study complements the previous study by examining the effects of fasting duration and insulin infusion on circulating levels of oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids. Northern elephant seal pups were studied at two post-weaning periods (n = 5/period): early fasting (1-2 weeks post-weaning; 127 ± 1 kg) and late fasting (6-7 weeks post-weaning; 93 ± 4 kg). Different cohorts of pups were weighed, sedated, and infused with 65 mU/kg of insulin. Plasma was collected prior to infusion (T0), and at 10, 30, 60, and 120 min post-infusion. A profile of ~80 oxylipins were analyzed by UPLC-ESI-MS/MS. Nine oxylipins changed between early and late fasting and eight were altered in response to insulin infusion. Fasting decreased PGF2a and increased 14,15-DiHETrE, 20-HETE, and 4-HDoHE (p<0.03) in T0 samples, while insulin infusion resulted in an inverse change in area under the curve (AUC) levels in these same metabolites (p<0.05). In addition, 12-HpETE and 12-HETE decreased with fasting and insulin infusion, respectively (p<0.04). The oxylipins altered during fasting and in response to insulin infusion may contribute to the manifestation of insulin resistance and participate in the metabolic regulation of associated cellular processes.


2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Jose Abraham Viscarra ◽  
Jose Pablo Vazquez‐Medina ◽  
Jacqueline Minas ◽  
Daniel E. Crocker ◽  
Rudy M. Ortiz

2013 ◽  
Vol 216 (17) ◽  
pp. 3215-3221 ◽  
Author(s):  
M. Suzuki ◽  
J. P. Vazquez-Medina ◽  
J. A. Viscarra ◽  
J. G. Sonanez-Organis ◽  
D. E. Crocker ◽  
...  

2010 ◽  
Vol 213 (14) ◽  
pp. 2524-2530 ◽  
Author(s):  
J. P. Vazquez-Medina ◽  
D. E. Crocker ◽  
H. J. Forman ◽  
R. M. Ortiz

2003 ◽  
Vol 178 (3) ◽  
pp. 533-539 ◽  
Author(s):  
RM Ortiz ◽  
DP Noren ◽  
CL Ortiz ◽  
F Talamantes

After nursing, pups of the northern elephant seal (Mirounga angustirostris) are approximately 46% body fat and rely almost entirely on the oxidation of their large fat stores to sustain their metabolism for the ensuing 8-12 week postweaning fast, which is a natural component of their life history. Thus, fasting pups provide an ideal opportunity to examine the hormonal alterations associated with prolonged food deprivation in a naturally adapted model. Cortisol, ghrelin, glucagon, growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, blood urea nitrogen (BUN), glucose and non-esterified fatty acids (NEFA) were examined in 20 male and 20 female pups blood sampled early (<1 week postweaning) and late (6-8 weeks postweaning) during the fast. Mean cortisol, ghrelin, GH, and glucagon increased 1.8-, 1.8-, 1.4-, and 2.3-fold between early and late periods, while mean IGF-I and insulin decreased 97% and 38%, respectively. NEFA increased 2.3-fold, while BUN and glucose decreased 46% and 11%, respectively. NEFA was significantly and positively correlated with cortisol and GH; individually; however, when the relationship was examined as a multiple regression the correlation improved suggesting that cortisol and GH act synergistically to promote lipolysis during the fast. GH and BUN were negatively and significantly correlated between early and late fasting suggesting that GH may promote protein sparing as well. The decrease in glucose may be responsible for stimulating glucagon, resulting in the maintenance of relative hyperglycemia. The increases in cortisol, ghrelin, glucagon, and GH suggest that these hormones may be integral in mediating the metabolism of seal pups during prolonged fasting.


2001 ◽  
Vol 281 (6) ◽  
pp. E1347-E1351 ◽  
Author(s):  
Rudy M. Ortiz ◽  
Dawn P. Noren ◽  
Beate Litz ◽  
C. Leo Ortiz

Many mammals seasonally reduce body fat due to inherent periods of fasting, which is associated with decreased leptin concentrations. However, no data exist on the correlation between fat mass (FM) and circulating leptin in marine mammals, which have evolved large fat stores as part of their adaptation to periods of prolonged fasting. Therefore, FM was estimated (by tritiated water dilution), and serum leptin and cortisol were measured in 40 northern elephant seal ( Mirounga angustirostris) pups early (<1 wk postweaning) and late (6–8 wk postweaning) during their natural, postweaning fast. Body mass (BM) and FM were reduced late; however, percent FM (early: 43.9 ± 0.5, late: 45.5 ± 0.5%) and leptin [early: 2.9 ± 0.1 ng/ml human equivalents (HE), late: 3.0 ± 0.1 ng/ml HE] did not change. Cortisol increased between early (9.2 ± 0.5 μg/dl) and late (16.3 ± 0.9 μg/dl) periods and was significantly and negatively correlated with BM ( r = 0.426; P < 0.0001) and FM ( r = 0.328; P = 0.003). FM and percent FM were not correlated ( P > 0.10) with leptin at either period. The present study suggests that these naturally obese mammals appear to possess a novel cascade for regulating body fat that includes cortisol. The lack of a correlation between leptin and FM may reflect the different functions of fat between terrestrial and marine mammals.


2017 ◽  
Vol 312 (2) ◽  
pp. R189-R196 ◽  
Author(s):  
Bridget Martinez ◽  
José G. Soñanez-Organis ◽  
José Arquimides Godoy-Lugo ◽  
Lillian J. Horin ◽  
Daniel E. Crocker ◽  
...  

Thyroid hormones (THs) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating THs that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity, suggesting that in mammals naturally adapted to prolonged fasting, THs are necessary to support metabolism. However, the functional relevance of this physiological paradox has remained largely unexplored, especially as it relates to the regulation of lipids. To address the hypothesis that TSH-mediated increase in THs contributes to lipid metabolism, we infused early and late-fasted pups with TSH and measured several key genes in adipose and muscle, and plasma hormones associated with regulation of lipid metabolism. TSH infusion increased the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) more than 6.5-fold at 60 min in muscle, and expression of uncoupling protein 2 (UCP2) more than 27-fold during the early fast at 60 min, in adipose. Additionally, during the late fast period, the protein content of adipose CD36 increased 1.1-fold, and plasma nonesterified fatty acid (NEFA) concentrations increased 25% at 120 min, with NEFA levels returning to baseline after 24 h. We show that the TSH-induced increases in THs in fasting pups are functional and likely contribute to the maintenance of a lipid-based metabolism.


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