Dehydrogenase In Adipose Tissue Research Articles

Genistein Induces Adipogenic and Autophagic Effects in Rainbow Trout (Oncorhynchus mykiss) Adipose Tissue: In Vitro and In Vivo Models.

Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 μM, and 1 μM 17β-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 μM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 μM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout.

Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11β-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11β-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancer-promoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11β-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser(660) HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome.

Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue.

The highly prevalent metabolic syndrome (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, along with abdominal obesity) resembles Cushing's syndrome. However, in simple obesity, plasma cortisol levels are not elevated. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), at least in mature adipocytes and hepatocytes, converts inactive circulating 11-keto steroids into active glucocorticoids, amplifying local glucocorticoid action. 11beta-HSD1 is elevated in adipose tissue in obese humans and rodents, suggesting that adipose tissue glucocorticoid excess may explain the conundrum. Indeed, transgenic mice overexpressing 11beta-HSD1 in adipose tissue faithfully replicate the metabolic syndrome. Conversely, 11beta-HSD1(-/-) mice resist the metabolic consequences of stress and high-fat feeding via insulin sensitisation and other advantageous effects in the liver and adipose tissue. Adipose 11beta-HSD1 deficiency contributes to a protective metabolic phenotype, supporting its role as a therapeutic target for the metabolic syndrome.

The Antiobesity Effect of Dehydroepiandrosterone in Rats

Initial studies showed that dehydroepiandrosterone (DHEA) treatment in mice resulted in lower body weight gain. Subsequent studies have shown that DHEA treatment in rats has a similar effect. In adult rodents, weight loss is a consequence of DHEA treatment. In general, these effects are independent of changes in food intake and are accompanied by lower body fat. DHEA treatment has been shown in some circumstances to alter a number of serum factors including glucose, insulin, cholesterol, and triacylglycerol. Recent studies have focused on the effects of DHEA on liver metabolism. Studies have been undertaken to determine whether the antiobesity effect of DHEA is mediated by the previously described inhibition of glucose-6-phosphate dehydrogenase by this steroid. It appears that inhibition of glucose-6-phosphate dehydrogenase in liver is not the initial metabolic response to DHEA but may play a contributing role. Inhibition of glucose-6-phosphate dehydrogenase in adipose tissue may affect differentiation of fat cells. A number of other enzymes involved in lipid and carbohydrate metabolism have also been shown to be altered by DHEA treatment, and several futile cycles involving some of these enzymes have been proposed to play a role in DHEA's antiobesity action. In addition, mitochondrial protein content is elevated by DHEA treatment. There appear to be time-dependent changes due to DHEA treatment on hepatic mitochondrial state three rates of respiration. Studies continue to evaluate the role of alterations in mitochondrial metabolism in DHEA's antiobesity action.

Insulin regulation of the activity and phosphorylation of branched-chain 2-oxo acid dehydrogenase in adipose tissue.

The activity of the intramitochondrial branched-chain 2-oxo acid dehydrogenase (BCDH), like that of pyruvate dehydrogenase, is regulated, at least in part, by interconversion between the active dephosphorylated enzyme and its inactive phosphorylated form. The stimulatory effect of insulin on BCDH activity was compared with its effect on phosphorylation of the enzyme. Intact tissues were incubated in the presence or the absence of insulin, and then mitochondria were isolated and disrupted before assaying for enzyme activity or estimating the extent of enzyme phosphorylation. Tissues were incubated in either the presence or the absence of leucine, which also stimulated BCDH activity up to 10-fold. Insulin (1 munit/ml) doubled the activity of BCDH in the absence and in the presence of leucine. Together, 1 mM-leucine and insulin appeared to stimulate BCDH activity fully. Phosphorylation of BCDH was estimated indirectly by measuring the incorporation of 32P into phosphorylation sites that remained unesterified after preparing mitochondrial extracts under conditions that preserved the effect of insulin on BCDH activity. Increased incorporation of 32P in these experiments implies decreased phosphorylation in situ when tissues were incubated with insulin and leucine. In the absence of leucine, little incorporation of 32P into BCDH was detected. In the presence of leucine, however, incorporation of 32P into BCDH was markedly increased, and insulin increased 32P incorporation still further. The results support the hypothesis that leucine and insulin both stimulate the activity of BCDH by promoting its dephosphorylation.

Insulin regulation of branched chain alpha-keto acid dehydrogenase in adipose tissue.

The enzyme which oxidizes alpha-keto[1-14C]isocaproate to 14CO2 is activated by incubation of adipose tissue segments with insulin. A 3-fold reduction in the apparent Km of the enzyme for alpha-ketoisocaproate was observed when homogenates of adipose tissue segments treated with insulin were compared to homogenates of control tissues. The enzyme was assayed at various times after homogenization of adipose tissue segments. Relatively small changes were observed in the activity from control or insulin-treated tissues for 30 min after homogenization. The persistence of the insulin effect after homogenization suggests that insulin may cause a covalent modification of the enzyme. The possibility that alpha-ketoisocaproate is oxidized by pyruvate dehydrogenase, which is also stimulated by insulin, is unlikely since the enzyme responsible for oxidation of 14C-labeled branched chain alpha-keto acids can be inactivated by heat at a rate distinct from that of pyruvate dehydrogenase. Moreover, unlabeled branched chain alpha-keto acids inhibit the oxidation of alpha-keto[1-14C]isocaproate but not that of [1-14C]pyruvate. Branched chain alpha-keto acid hydrogenase can be activated by incubation of adipose tissue homogenates in the presence of magnesium chloride and in the absence of ATP. The addition of ATP plus an ATP-regenerating system reverses the activation of the enzyme. The apparent Km of the enzyme is reduced and the Vmax is increased by incubation of tissue extracts under appropriate conditions.

Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats.

Plasma insulin concentrations in fed rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in adipose tissue and liver were estimated from the incorporation of 3H from 3H2O. In the adipose tissue dehydrogenase and acetyl-CoA carboxylase were evident. In liver, although changes in rates of fatty acid synthesis were found, the initial activity of pyruvate dehydrogenase did not alter, but small parallel changes in acetyl-CoA carboxylase activity were observed.

Activation of pyruvate dehydrogenase in adipose tissue by insulin. Evidence for an effect of insulin on pyruvate dehydrogenase phosphate phosphatase

1. The mechanism by which insulin activates pyruvate dehydrogenase in rat epididymal adipose tissue was further investigated. 2. When crude extracts, prepared from tissue segments previously exposed to insulin (2m-i.u/ml) for 2min, were supplemented with Mg-2+, Ca-2+, glucose and hexokinase and incubated at 30 degrees C, they displayed an enhanced rate of increase in pyruvate dehydrogenase activity compared with control extracts. 3. When similar extracts were instead supplemented with fluoride, ADP, creatine phosphate and creatine kinase, the rate of decrease in pyruvate dehydrogenase activity observed during incubation at 30 degrees C was unaffected by insulin treatment. 4. It is suggested that insulin increases the fraction of pyruvate dehydrogenase present in the tissue in the active dephospho form by increasing the activity of pyruvate dehydrogenase phosphate phosphatase.

Activation of pyruvate dehydrogenase in adipose tissue: role of insulin and pyruvate.

This study was designed to investigate the relation between activation of pyruvate dehydrogenase in white adipose tissue and the intracellular pyruvate content. The intracellular pyruvate level was approximately 8 nmol/g wet weight when adipose tissue was incubated up to 20 min with fructose (1 mg/ml) as substrate. The addition of insulin to the incubation medium resulted in a 1.5-fold increase in the active form of pyruvate dehydrogenase after 20 min incubation without raising the intracellular pyruvate level at earlier time periods. Intracellular pyruvate contents were increased 1.5-fold by TMPD (75 μM), but in this case there was no concomitant activation of pyruvate dehydrogenase. We conclude that the insulin-induced activation of pyruvate dehydrogenase is caused by mechanism(s) in addition to an elevation of pyruvate concentration.

Alpha-glycerophosphate dehydrogenase and glucose-6-phosphate dehydrogenase in tissues of the Weddell seal.

High activity of alpha-glycerophosphate dehydrogenase and low activity of glucose-6-phosphate dehydrogenase in adipose tissue of Weddell seals suggest that neutral fat may be assembled there from exogenous sources of fatty acids. Low activity of glucose-6-phosphate dehydrogenase in other tissues tested precludes assignment of the function of fatty-acid synthesis to any specific tissue and emphasizes uniqueness of adipose mass in seals.

Lipogenesis in adipose tissue of meal-fed rats. A possible regulatory role of alpha-glycerophosphate formation.

The incorporation of acetate-1-14C into fatty acids by isolated epididymal adipose tissue of fed and fasted rats adapted to a single daily 2-hour meal (meal eaters) or fed ad libitum (nibblers) was investigated. Fasting (22 hours) markedly depressed lipogenesis whereas fatty acid synthesis increased linearly with time of refeeding in meal-fed but not in nibbling rats. The activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-malic dehydrogenase in adipose tissue of meal-fed or nibbling rats were not altered as a consequence of a 22-hour fast or of subsequent feeding for 2 hours. The incorporation of acetate-1-l4C into fatty acids by adipose tissue of fasted meal-eating or nibbling animals was markedly enhanced by the addition of unlabeled pyruvate or oxaloacetate to the incubation medium. This stimulatory effect was not observed with adipose tissue front fed meal-eating rats. The addition of unlabeled glucose and insulin to the incubation medium markedly enhanced acetate-1-14C incorporation into fatty acids by isolated adipose tissue and completely overcame any effect of fasting. Adipose tissue converted pyruvate-1-14C, -2-14C, or -3-14C to fatty acids and glyceride-glycerol. The results obtained are consistent with the functioning of a pathway in adipose tissue involving mitochondrial carboxylation of pyruvate to oxaloacetate, and equilibration of the newly formed oxaloacetate with malate and fumarate, followed by cytoplasmic conversion of oxaloacetate to phosphoenol pyruvate. The data are interpreted to support a control mechanism in which fatty acid synthesis is inhibited by tissue fatty acids and fatty acyl-CoA derivatives. The inhibition could in turn be reduced by the availability of α-glycerophosphate, for the esterification of fatty acids. This control mechanism is proposed as the explanation for the refeeding response observed in adipose tissue of meal-fed rats.

Fatty acid dehydrogenase in adipose tissue

Research Article| April 01 1943 Fatty acid dehydrogenase in adipose tissue B. Shapiro; B. Shapiro 1Department of Pathological Physiology, The Hebrew University, Jerusalem Search for other works by this author on: This Site PubMed Google Scholar E. Wertheimer E. Wertheimer 1Department of Pathological Physiology, The Hebrew University, Jerusalem Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1943) 37 (1): 102–104. https://doi.org/10.1042/bj0370102 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation B. Shapiro, E. Wertheimer; Fatty acid dehydrogenase in adipose tissue. Biochem J 1 April 1943; 37 (1): 102–104. doi: https://doi.org/10.1042/bj0370102 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1943 CAMBRIDGE UNIVERSITY PRESS1943 Article PDF first page preview Close Modal You do not currently have access to this content.