EFFECT OF SOMATOSTATIN AND CHRONIC COLD EXPOSURE ON HORMONAL AND METABOLITE CONCENTRATION, METABOLIC RATE, THERMOREGULATION, AND GUT MOTILITY IN SHEEP

1990 ◽  
Vol 70 (4) ◽  
pp. 1073-1083 ◽  
Author(s):  
R. A. CHRISTENSEN ◽  
R. J. CHRISTOPHERSON ◽  
J. J. KENNELLY

The effect of somatostatin-14 (SS-14) (6.7 ng min−1 kg−1 BW) on hormone and metabolite concentrations, gastrointestinal motility, thermoregulation, and heat production was studied in five ewe lambs (45.8 ± 2.8 kg BW) adapted to either thermoneutral (TN) (17.4 °C) or chronic cold (CC) (− 0.9 °C). Lambs received a barley:soybean diet at 25.6 g DM d−1 kg−1 BW. Environmental temperature and SS-14 infusion had no effect on the frequency or duration of components of the duodenal migrating myoelectric complex (MMC), although cold exposure increased (P < 0.05) total number of contractions within the MMC. CC increased (P < 0.05) heat production by 41%, while SS-14 decreased (P < 0.05) heat production by 4% in both environments. Plasma concentrations of free fatty acids (P < 0.05) were increased during cold exposure. In response to SS-14 infusion plasma free fatty acid levels increased (P < 0.05) in the TN environment, while their level declined in the cold environment. Growth hormone, glucagon, and insulin concentrations were not influenced by cold exposure or SS-14 infusion. CC increased plasma T3 concentration but this response was abolished by SS-14. Thus, in lambs fed a concentrate diet, somatostatin at low doses slightly reduces whole body metabolism, possibly by an influence on thyroid hormones. Key words: Cold, somatostatin, gastrointestinal motility, sheep, metabolism, thyroid

1991 ◽  
Vol 71 (4) ◽  
pp. 1079-1086 ◽  
Author(s):  
R. A. Christensen ◽  
J. J. Kennelly ◽  
R. J. Christopherson

Effects of intrajugular infusions of somatostatin-14 (SS-14) (8.9, 18.4, and 37.3 ng min−1 kg−1 BW) or saline were studied in three acutely (2 h) cold-stressed (0 °C) ewe lambs (39.8 ± 1.8 kg BW) fed a barley soybean meal diet at 25.6 g DM d−1 kg−1 BW. Acute cold exposure transiently increased (P < 0.001) and rewarming decreased (P < 0.001) recticular contraction frequency, with no effect of SS-14. The duration of duodenal irregular spiking activity was decreased (P < 0.05) by SS-14 at doses of 18.3 and 37.3 ng min−1 kg−1 and was not affected by cold exposure. This resulted in a decrease (P < 0.05) in the average duration of the individual migrating myoelectric complex. Cold exposure increased (P < 0.01) plasma concentration of free fatty acids (FFA). Orthogonal contrasts of the changes during somatostatin infusion indicated linear increases in glucose and linear and cubic increases in FFA concentrations in plasma (P < 0.05). Infusion of somatostatin had no effect on basal concentrations of growth hormone, insulin, or glucagon but produced linear reductions in plasma insulin and glucagon responses during cold exposure (P < 0.05). Somatostatin modestly influenced hormone and metabolite concentration during acute cold exposure without apparent effect on body temperature. Key words: Cold, somatostatin, sheep, gastrointestinal motility, glucagon, insulin


1990 ◽  
Vol 115 (3) ◽  
pp. 421-428 ◽  
Author(s):  
M. E. Symonds ◽  
M. A. Lomax

SUMMARYMuscle metabolism was studied in pregnant sheep over the final 4 weeks of pregnancy, between January and March 1985 and between December and March 1986, to investigate the effect of (i) chronic cold exposure, induced by shearing pregnant ewes 8 weeks before lambing and (ii) undernutrition in shorn and unshorn ewes. This was achieved by measuring hind-limb tissue metabolism using a combination of isotopic and arterio–venous difference techniques.The rates of blood flow, oxygen uptake, carbon dioxide production and calculated heat production were all significantly higher across the hind-limb tissues in shorn than in unshorn ewes. The increase in hind-limb energy metabolism in the shorn group was such that 65% of the difference in wholebody heat production between shorn and unshorn groups could be attributed to muscle tissue. Following underfeeding, all of the difference in whole-body heat production between the two groups was completely attributable to muscle tissue.Nonesterified fatty acid (NEFA) oxidation by muscle accounted for 46% of the difference in whole-body NEFA oxidation rate between fed shorn and unshorn groups. Underfeeding significantly increased the mean arterial plasma concentration of NEFA in shorn and unshorn ewes and the rate of NEFA oxidation across the hind-limb tissues in shorn ewes. The difference in whole-body NEFA oxidation between shorn and unshorn groups could, therefore, be completely accounted for by muscle. No significant differences in the arterial plasma concentrations of glucose, lactate or 3-hydroxybutyrate were recorded between shorn and unshorn ewes, although the rate of glucose uptake across the hind-limb tissued was significantly higher in the shorn group. Calculation of the maximum potential contribution of these substrates to hind-limb metabolism demonstrated that NEFA were the predominant energy source in all experimental conditions studied in all ewes. When data from fed and underfed shorn ewes were pooled, regression analysis revealed a significant negative correlation between the arterial plasma concentrations of glucose and 3-hydroxybutyrate, and significant positive relationships between the arterial concentrations of both glucose and 3-hydroxybutyrate and their rate of uptake across the hind-limb tissues. These relationsips were not observed in unshorn ewes.It is concluded that the muscle mass plays a major role in the nonshivering thermogenic adaptation to chronic cold exposure in shorn pregnant sheep and that NEFA are the major substrate utilized for oxidative metabolism in this tissue.


2018 ◽  
Vol 238 (2) ◽  
pp. 91-106 ◽  
Author(s):  
Aldo Grefhorst ◽  
Johanna C van den Beukel ◽  
Wieneke Dijk ◽  
Jacobie Steenbergen ◽  
Gardi J Voortman ◽  
...  

Cold exposure of mice is a common method to stimulate brown adipose tissue (BAT) activity and induce browning of white adipose tissue (WAT) that has beneficial effects on whole-body lipid metabolism, including reduced plasma triglyceride (TG) concentrations. The liver is a key regulatory organ in lipid metabolism as it can take up as well as oxidize fatty acids. The liver can also synthesize, store and secrete TGs in VLDL particles. The effects of cold exposure on murine hepatic lipid metabolism have not been addressed. Here, we report the effects of 24-h exposure to 4°C on parameters of hepatic lipid metabolism of male C57BL/6J mice. Cold exposure increased hepatic TG concentrations by 2-fold (P < 0.05) but reduced hepatic lipogenic gene expression. Hepatic expression of genes encoding proteins involved in cholesterol synthesis and uptake such as the LDL receptor (LDLR) was significantly increased upon cold exposure. Hepatic expression of Cyp7a1 encoding the rate-limiting enzyme in the classical bile acid (BA) synthesis pathway was increased by 4.3-fold (P < 0.05). Hepatic BA concentrations and fecal BA excretion were increased by 2.8- and 1.3-fold, respectively (P < 0.05 for both). VLDL-TG secretion was reduced by approximately 50% after 24 h of cold exposure (P < 0.05). In conclusion, cold exposure has various, likely intertwined effects on the liver that should be taken into account when studying the effects of cold exposure on whole-body metabolism.


2019 ◽  
Vol 126 (6) ◽  
pp. 1598-1606 ◽  
Author(s):  
Kyle Gordon ◽  
Denis P. Blondin ◽  
Brian J. Friesen ◽  
Hans Christian Tingelstad ◽  
Glen P. Kenny ◽  
...  

Daily compensable cold exposure in humans reduces shivering by ~20% without changing total heat production, partly by increasing brown adipose tissue thermogenic capacity and activity. Although acclimation and acclimatization studies have long suggested that daily reductions in core temperature are essential to elicit significant metabolic changes in response to repeated cold exposure, this has never directly been demonstrated. The aim of the present study is to determine whether daily cold-water immersion, resulting in a significant fall in core temperature, can further reduce shivering intensity during mild acute cold exposure. Seven men underwent 1 h of daily cold-water immersion (14°C) for seven consecutive days. Immediately before and following the acclimation protocol, participants underwent a mild cold exposure using a novel skin temperature clamping cold exposure protocol to elicit the same thermogenic rate between trials. Metabolic heat production, shivering intensity, muscle recruitment pattern, and thermal sensation were measured throughout these experimental sessions. Uncompensable cold acclimation reduced total shivering intensity by 36% ( P = 0.003), without affecting whole body heat production, double what was previously shown from a 4-wk mild acclimation. This implies that nonshivering thermogenesis increased to supplement the reduction in the thermogenic contribution of shivering. As fuel selection did not change following the 7-day cold acclimation, we suggest that the nonshivering mechanism recruited must rely on a similar fuel mixture to produce this heat. The more significant reductions in shivering intensity compared with a longer mild cold acclimation suggest important differential metabolic responses, resulting from an uncompensable compared with compensable cold acclimation. NEW & NOTEWORTHY Several decades of research have been dedicated to reducing the presence of shivering during cold exposure. The present study aims to determine whether as little as seven consecutive days of cold-water immersion is sufficient to reduce shivering and increase nonshivering thermogenesis. We provide evidence that whole body nonshivering thermogenesis can be increased to offset a reduction in shivering activity to maintain endogenous heat production. This demonstrates that short, but intense cold stimulation can elicit rapid metabolic changes in humans, thereby improving our comfort and ability to perform various motor tasks in the cold. Further research is required to determine the nonshivering processes that are upregulated within this short time period.


2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.


GeroScience ◽  
2021 ◽  
Author(s):  
Haihui Zhuang ◽  
Sira Karvinen ◽  
Timo Törmäkangas ◽  
Xiaobo Zhang ◽  
Xiaowei Ojanen ◽  
...  

AbstractAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial β-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.


2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.


2021 ◽  
Author(s):  
Diana Abu Halaka ◽  
Ofer Gover ◽  
Einat Rauchbach ◽  
Shira Zelber-Sagi ◽  
Betty Schwartz ◽  
...  

Nitrites and nitrates are traditional food additives used as curing agents in the food industry. They inhibit the growth of microorganisms and convey a typical pink color to the meat....


1971 ◽  
Vol 49 (5) ◽  
pp. 394-398 ◽  
Author(s):  
W. D. Wagner ◽  
R. A. Peterson ◽  
R. J. Cenedella

Plasma free fatty acid (FFA) levels and the effects of prostaglandin E1 (PGE1) were studied in cold-acclimated and cold-exposed chickens and compared to controls. Chickens cold-acclimated at 4–7 or 8–11 °C for 4 weeks had significantly elevated plasma FFA when compared to the controls at 19–21 °C. Although PGE1 had no effect on the basal level of FFA of controls, a significantly lower plasma FFA was seen after injection of either 10 or 30 μg PGE1/kg in cold-acclimated chickens. Chickens cold-exposed to 2–3 °C for 4 h demonstrated significant elevations of plasma FFA when compared to controls. Only 30 μg PGE1/kg significantly depressed the plasma FFA in the cold-exposed birds. No inhibition of basal FFA release was seen in control animals. From these experiments, it is concluded that chickens mobilize FFA extensively under cold-exposure and that this stimulated lipolysis is inhibited by PGE1.


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