Effects of adrenergic agonists and antagonists on the metabolism of [1-14C]oleic acid by rat hepatocytes

Olubadewo, Joseph O.; Heimberg, Murray

doi:10.1016/0006-2952(93)90225-l

Cited by 3 publications

(5 citation statements)

References 37 publications

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“…After an overnight fast, mice were anesthetized with pentobarbital (50 mg kg −1 ) and the liver removed. We used a Staddie-Riggs microtome to obtain fresh liver slices (~0.5 mm thick) that were immediately weighed and incubated for 1 h under 95% O 2 :5% CO 2 in Krebs-Henseleit buffer containing 5.5 mM glucose and a 3% BSA/1 mM 14 C-oleic acid complex 27 . The final specific activity was 250,000 dpm µmol −1 .…”

Section: Metabolism Of 14 C-oleate In Liver Slicesmentioning

confidence: 99%

“…The final specific activity was 250,000 dpm µmol −1 . We determined 14 CO 2 production using hyamine hydroxide to trap the CO 2 and measuring the radioactive counts in a liquid scintillation spectrometer essentially as described 27 . The 14 C-oleic acid incorporation into ketone bodies and secreted triglycerides was determined in the liver slice incubations under similar conditions, except the cells were continuously gassed with 95% O 2 :5% CO 2 and no hyamine hydroxide was used.…”

Section: Metabolism Of 14 C-oleate In Liver Slicesmentioning

confidence: 99%

“…After the 40-min incubation, we removed the media for extraction of lipids and ketone bodies. We measured the radioactivity incorporated into ketone bodies after perchloric acid deproteinization as described 27 . The triglycerides were separated from media lipid extracts by thin layer chromatography, and the radioactivity in the band corresponding to triglycerides was determined as previously described 28 .…”

Section: Metabolism Of 14 C-oleate In Liver Slicesmentioning

confidence: 99%

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Positional cloning of the combined hyperlipidemia gene Hyplip1

et al. 2001

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Familial combined hyperlipidemia (FCHL, MIM-144250) is a common, multifactorial and heterogeneous dyslipidemia predisposing to premature coronary artery disease and characterized by elevated plasma triglycerides, cholesterol, or both. We identified a mutant mouse strain, HcB-19/Dem (HcB-19), that shares features with FCHL, including hypertriglyceridemia, hypercholesterolemia, elevated plasma apolipoprotein B and increased secretion of triglyceride-rich lipoproteins. The hyperlipidemia results from spontaneous mutation at a locus, Hyplip1, on distal mouse chromosome 3 in a region syntenic with a 1q21-q23 FCHL locus identified in Finnish, German, Chinese and US families. We fine-mapped Hyplip1 to roughly 160 kb, constructed a BAC contig and sequenced overlapping BACs to identify 13 candidate genes. We found substantially decreased mRNA expression for thioredoxin interacting protein (Txnip). Sequencing of the critical region revealed a Txnip nonsense mutation in HcB-19 that is absent in its normolipidemic parental strains. Txnip encodes a cytoplasmic protein that binds and inhibits thioredoxin, a major regulator of cellular redox state. The mutant mice have decreased CO2 production but increased ketone body synthesis, suggesting that altered redox status down-regulates the citric-acid cycle, sparing fatty acids for triglyceride and ketone body production. These results reveal a new pathway of potential clinical significance that contributes to plasma lipid metabolism.

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Section: Metabolism Of 14 C-oleate In Liver Slicesmentioning

confidence: 99%

Section: Metabolism Of 14 C-oleate In Liver Slicesmentioning

confidence: 99%

Section: Metabolism Of 14 C-oleate In Liver Slicesmentioning

confidence: 99%

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Positional cloning of the combined hyperlipidemia gene Hyplip1

et al. 2001

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“…Glucocorticoids (Pilkis and Granner, 1992;Edgerton et al, 2006) and the adrenergic system (Goodhardt et al, 1984;Apatu and Barnes, 1991;Fowden and Forhead, 2011) stimulate eGP and may also affect FA oxidation (Olubadewo and Heimberg, 1993;Lettéron et al, 1997) and triacylglyceride storage in liver (Vegiopoulos and Herzig, 2007;Rose et al, 2010). In calves, β-adrenergic agonists stimulated glycogenolysis and fat mobilization in a dose-dependent manner (Blum and Flueckiger, 1988), whereas treatment with dexamethasone, a potent glucocorticoid, failed to stimulate postnatal eGP, but provoked peripheral insulin resistance Scheuer et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Catecholamines and the adrenergic system play a pivotal role in perinatal maturation of metabolic processes in the liver related to energy supply (e.g., eGP; Apatu and Barnes, 1991;Fowden and Forhead, 2011) and FA oxidation (Olubadewo and Heimberg, 1993) in neonates, including calves (Hammon et al, 2012(Hammon et al, , 2013. Plasma concentrations of adrenaline and noradrenaline are elevated around birth and support metabolic adaptation for postnatal life (Eliot et al, 1981;Richet et al, 1985;Hume et al, 2005).…”

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confidence: 99%

Effects of colostrum versus formula feeding on hepatic glucocorticoid and α1- and β2-adrenergic receptors in neonatal calves and their effect on glucose and lipid metabolism

Schäff

Rohrbeck

Steinhoff‐Wagner

et al. 2014

Journal of Dairy Science

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Neonatal energy metabolism in calves has to adapt to extrauterine life and depends on colostrum feeding. The adrenergic and glucocorticoid systems are involved in postnatal maturation of pathways related to energy metabolism and calves show elevated plasma concentrations of cortisol and catecholamines during perinatal life. We tested the hypothesis that hepatic glucocorticoid receptors (GR) and α 1 -and β 2 -adrenergic receptors (AR) in neonatal calves are involved in adaptation of postnatal energy metabolism and that respective binding capacities depend on colostrum feeding. Calves were fed colostrum (CF; n = 7) or a milk-based formula (FF; n = 7) with similar nutrient content up to d 4 of life. Blood samples were taken daily before feeding and 2 h after feeding on d 4 of life to measure metabolites and hormones related to energy metabolism in blood plasma. Liver tissue was obtained 2 h after feeding on d 4 to measure hepatic fat content and binding capacity of AR and GR. Maximal binding capacity and binding affinity were calculated by saturation binding assays using [3 H]-prazosin and [ 3 H]-CGP-12177 for determination of α 1 -and β 2 -AR and [ 3 H]-dexamethasone for determination of GR in liver. Additional liver samples were taken to measure mRNA abundance of AR and GR, and of key enzymes related to hepatic glucose and lipid metabolism. Plasma concentrations of albumin, triacylglycerides, insulin-like growth factor I, leptin, and thyroid hormones changed until d 4 and all these variables except leptin and thyroid hormones responded to feed intake on d 4. Diet effects were determined for albumin, insulin-like growth factor I, leptin, and thyroid hormones. Binding capacity for GR was greater and for α 1 -AR tended to be greater in CF than in FF calves. Binding affinities were in the same range for each receptor type. Gene expression of α 1 -AR (ADRA1) tended to be lower in CF than FF calves. Binding capacity of GR was related to parameters of glucose and lipid metabolism, whereas β 2 -AR binding capacity was negatively associated with glucose metabolism. In conclusion, our results indicate a dependence of GR and α 1 -AR on milk feeding immediately after birth and point to an involvement of hepatic GR and AR in postnatal adaptation of glucose and lipid metabolism in calves.

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Metabolic effects of antihypertensive agents: role of sympathoadrenal and renin-angiotensin systems

Ernsberger

Koletsky

2006

Naunyn-Schmied Arch Pharmacol

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Reports of beneficial, neutral and adverse impacts of antihypertensive drug classes on glucose and lipid metabolism can be found in human data. Furthermore, mechanisms for these diverse effects are often speculative and controversial. Clinical trial data on the metabolic effects of antihypertensive agents are highly contradictory. Comparisons of clinical trials involving different agents are complicated by differences in the spectrum of metabolic disturbances that accompany hypertension in different groups of patients. Two physiological systems are predominant at the interface between metabolic and cardiovascular regulation: the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). These two systems are major targets of antihypertensive drug actions, and also mediate many of the beneficial and adverse effects of antihypertensive agents on glucose and lipid metabolism. Thiazides and beta-adrenergic antagonists can adversely affect glucose and lipid metabolism, which are frequently compromised in human essential hypertension, and increase the incidence of new cases of diabetes. Laboratory studies confirm these effects, and suggest that compensatory activation of the SNS and RAS may be one mechanism. Other antihypertensives directly targeting the SNS and RAS may have beneficial effects on glucose and lipid metabolism, and may prevent diabetes. Resolution of the controversies surrounding the metabolic effects of antihypertensive agents can only be resolved by further laboratory studies, in addition to controlled clinical trials.

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Effects of adrenergic agonists and antagonists on the metabolism of [1-14C]oleic acid by rat hepatocytes

Cited by 3 publications

References 37 publications

Positional cloning of the combined hyperlipidemia gene Hyplip1

Positional cloning of the combined hyperlipidemia gene Hyplip1

Effects of colostrum versus formula feeding on hepatic glucocorticoid and α1- and β2-adrenergic receptors in neonatal calves and their effect on glucose and lipid metabolism

Metabolic effects of antihypertensive agents: role of sympathoadrenal and renin-angiotensin systems

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