scholarly journals Oxylipin Responses to Fasting and Insulin Infusion in a Large Mammalian Model of Fasting-Induced Insulin Resistance, the Northern Elephant Seal

2021 ◽  
Author(s):  
Dana N. Wright ◽  
Kondwani G.H. Katundu ◽  
Jose A. Viscarra ◽  
Daniel E. Crocker ◽  
John W. Newman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Metabolic Regulation ◽  
Insulin Infusion ◽  
Area Under The Curve ◽  
Elephant Seal ◽  
Bioactive Metabolites ◽  
Northern Elephant Seal ◽  
Post Infusion ◽  
Fasting Duration

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.

Gamma-oryzanol Ameliorates Insulin Resistance and Hyperlipidemia in Rats with Streptozotocin/nicotinamide-induced Type 2 Diabetes

2010 ◽  
Vol 80 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Hsing-Hsien Cheng ◽  
Chien-Ya Ma ◽  
Tsui-Wei Chou ◽  
Ya-Yen Chen ◽  
Ming-Hoang Lai
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Rice Bran Oil ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
Negative Influence ◽  
Control Group ◽  
Gamma Oryzanol

Gamma-oryzanol is a component of rice bran oil (RBO) with purported health benefits. This study evaluated the effects of gamma-oryzanol on insulin resistance and lipid metabolism in Wistar rats with type 2 diabetes (T2DM). The rats were divided into three groups and consumed one of the following diets for 5 weeks: 15 % soybean oil (control group); 15 % palm oil (PO); and 15 % PO with the addition of 5.25 g gamma-oryzanol (POO). The results showed that PO markedly increased plasma low-density-lipoprotein cholesterol, plasma triglycerides, and hepatic triglyceride levels, but did not reduce the area under the curve for glucose and insulin significantly, compared with the control group. Adding gamma-oryzanol to PO improved the negative influence of PO on lipid metabolism in T2DM rats. In addition, gamma-oryzanol tended to increase insulin sensitivity in T2DM rats compared to control and PO groups. Longer-term studies are needed to evaluate these effects further.

Relationships between plasma ketones and fasting duration in neonatal elephant seals

1990 ◽  
Vol 259 (5) ◽  
pp. R1086-R1089 ◽  
Author(s):  
M. A. Castellini ◽  
D. P. Costa
Keyword(s):  
Ketone Bodies ◽  
Elephant Seal ◽  
Northern Elephant Seal ◽  
Elephant Seals ◽  
Long Duration ◽  
Fat Stores ◽  
Low Levels ◽  
Beta Hydroxybutyrate ◽  
Fasting Duration ◽  
Circulating Levels

Long-duration fasting in mammals can ultimately lead to stage three terminal starvation, which is characterized by depleted fat stores, a metabolic shift away from fat metabolism toward lean tissue catabolism, and a sharp decline in circulating levels of plasma fatty acids and ketone bodies. However, this biochemical shift has never been observed outside of the laboratory in a naturally fasting, nonhibernating mammal. In the current study, plasma levels of the ketone body D-beta-hydroxybutyrate (beta-HBA) were assayed in 10 Northern elephant seal pups during suckling and the postweaning fast and in 12 fasting adult seals. Plasma beta-HBA concentration in the pups was minimal during suckling (0.09 +/- 0.06 mM; n = 10) and began to increase immediately after weaning. The concentration rose until about 55 days into the fast (1.34 +/- 0.36 mM; n = 10) and then declined sharply. Within 10 days of this deflection point, the seal pups left for sea. By contrast, adult elephant seals showed consistently low levels of beta-HBA after several months of fasting (0.06 +/- 0.07 mM; n = 12). The data suggest that the duration of fasting in elephant seal pups may be determined, in part, by biochemical shifts that occur near the end of the fast and that the regulation of ketone concentration is different in fasting neonatal and adult elephant seals.

scholarly journals Thyroid hormone-stimulated increases in PGC-1α and UCP2 promote life history-specific endocrine changes and maintain a lipid-based metabolism

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 ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Uncoupling Protein ◽  
Elephant Seal ◽  
Nonesterified Fatty Acid ◽  
Peroxisome Proliferator ◽  
Prolonged Fasting ◽  
Northern Elephant Seal ◽  
Apparent Paradox ◽  
Peroxisome Proliferator Activated Receptor ◽  
Functional Relevance

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.

Acromegaly and insulin resistance: a case study

1986 ◽  
Vol 111 (4) ◽  
pp. 445-451 ◽  
Author(s):  
J. M. Garía López ◽  
A. De La Fuente ◽  
Ma A. Tomé ◽  
J. A. Mato Mato ◽  
G. Juan Gaudiero ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Plasma Levels ◽  
Insulin Infusion ◽  
Blood Glucose Concentration ◽  
Area Under The Curve ◽  
Straight Line ◽  
Extracellular Glucose ◽  
Time Required

Abstract. Elevated levels of growth hormone (GH) alter both the glucose tolerance and the sensitivity of peripheral tissue to insulin. We have studied the relationship between impaired glucose metabolism and its variations with different plasma levels of endogenous GH in one patient with acromegaly. To do so, we studied the decline in blood glucose concentration, as induced by iv insulin infusion, from a given hyperglycaemic level. With high levels of GH (GH = 120 μg/l), the slope of the straight line representing the decrease in blood glucose after insulin infusion was —0.71, the time required to achieve normoglycaemic levels, 270 min, and the corrected area under the curve representing blood glucose 26070 units2. After 10 months' bromocriptine treatment, GH plasma concentration fell to 8 μg/l, at which point the slope of the straight line was —1.40, the time required to achieve normoglycaemic levels 115 min, and the area under the curve 8956 units2. There was a greater total clearance of glucose when GH levels were lower (1.90 vs 1.00 ml/min/kg), as well as greater elimination of glucose from the extracellular glucose pool (4.02 vs 1.67 mg/min/kg). In conclusion, in this patient the elevated plasma levels of endogenous GH induced insulin resistance. Once GH levels were reduced by the administration of bromocriptine, glucose metabolism improved.

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