Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Rats were made hypothyroid by feeding them with propylthiouracil together with a low-iodine diet for 4 weeks. 2. [U-14C]Glucose conversion into fatty acids was substantially enhanced in brown adipocytes isolated from hypothyroid rats. Incorporation of 3H2O into fatty acids in vivo was enhanced in hypothyroidism in interscapular brown fat, but not in epididymal white fat or in liver. Hypothyroidism increased the activities of fatty acid synthase and ATP citrate lyase in brown, but not in white, adipocytes. 3. Glycolytic flux in brown adipocytes, quantified by [3-3H]glucose detritiation, was increased by hypothyroidism. This change was accompanied by increased maximum activity of phosphofructokinase. In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells. It is suggested that in the brown adipocyte the overall conversion of glucose into fatty acids is enhanced in thyroid deficiency, but that this change is muted in the white adipocyte, possibly because of limitation of glucose transport. 4. Fatty acid synthesis in brown adipocytes from hypothyroid animals was considerably less sensitive to inhibition by exogenous fatty acids than is the process in cells from euthyroid animals. Consequently, the effect of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acid.
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PMID:A tissue-specific increase in lipogenesis in rat brown adipose tissue in hypothyroidism. 304 65

1. Brown adipocytes were isolated from the interscapular depot of male rats maintained at approx. 21 degrees C. In some experiments parallel studies were made with white adipocytes from the epididymal depot. 2. Insulin increased and noradrenaline decreased [U-14C]glucose incorporation into fatty acids by brown adipocytes. Brown adipocytes differed from white adipocytes in that exogenous fatty acid (palmitate) substantially decreased fatty acid synthesis from glucose. Both noradrenaline and insulin increased lactate + pyruvate formation by brown adipocytes. Brown adipocytes converted a greater proportion of metabolized glucose into lactate + pyruvate and a smaller proportion into fatty acids than did white adipocytes. 3. In brown adipocytes, when fatty acid synthesis from [U-14C]glucose was decreased by noradrenaline or palmitate, incorporation of 3H2O into fatty acids was also decreased to an extent which would not support proposals for extensive recycling into fatty acid synthesis of acetyl-CoA derived from fatty acid oxidation. 4. In the absence of glucose, [U-14C]lactate was a poor substrate for lipogenesis in brown adipocytes, but its use was facilitated by glucose. When brown adipocytes were incubated with 1 mM-lactate + 5 mM-glucose, lactate-derived carbon generally provided at least 50% of the precursor for fatty acid synthesis. 5. Both insulin and noradrenaline increased [U-14C]glucose conversion into CO2 by brown adipocytes (incubated in the presence of lactate) and, in combination, stimulation of glucose oxidation by these two agents showed synergism. Rates of 14CO2 formation from glucose by brown adipocytes were relatively small compared with maximum rates of oxygen consumption by these cells, suggesting that glucose is unlikely to be a major substrate for thermogenesis. 6. Brown adipocytes from 6-week-old rats had considerably lower maximum rates of fatty acid synthesis, relative to cell DNA content, than white adipocytes. By contrast, rates of fatty acid synthesis from 3H2O in vivo were similar in the interscapular and epididymal fat depots. Expressed relative to activities of fatty acid synthase or ATP citrate lyase, however, brown adipocytes synthesized fatty acids as effectively as did white adipocytes. It is suggested that the cells most active in fatty acid synthesis in the brown adipose tissue are not recovered fully in the adipocyte fraction during cell isolation. Differences in rates of fatty acid synthesis between brown and white adipocytes were less apparent at 10 weeks of age.
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PMID:Lipogenesis in rat brown adipocytes. Effects of insulin and noradrenaline, contributions from glucose and lactate as precursors and comparisons with white adipocytes. 313 22

As previously reported, preadipocytes cloned from the epididymal fat of lean or genetically obese mice (HGFu and ob 17, respectively) contain the nuclear T3 receptor. The number of receptor sites was similar in confluent cells of both lines and approximately doubled during adipocyte differentiation. T3 added to the culture medium increased triacylglycerol synthesis. T3 also increased fatty acid synthase specific activity, relative synthesis rate, and relative mRNA content (1.5- to 2.5-fold). Optimal responses were obtained at 1.5 nM. This study shows that under the same culture conditions in both cell lines, 1.5 nM T3 decreased the receptor concentration with no significant change in the affinity for T3. The receptor depletion was time dependent, rapid, stable in the presence of T3, and reversible in less than 24 h after its withdrawal. Receptor depletion was also dependent on T3 concentration and close to maximum at 1.5 nM T3 [45.1 +/- 2.7% (+/- SE) of the data values without T3; n = 14]. A linear relationship was observed between receptor occupancy by T3 and receptor loss. T4 and triiodothyroacetic acid also decreased the T3 receptor content, as expected from their own affinity for the receptor. These last two observations suggest that the receptor reduction is related to its occupancy by T3. The reported results, also observed in several other cell types, indicate that down-regulation of the nuclear T3 receptor by thyroid hormones is probably a generalized event in T3 target cells at least in vitro. Interpretation of its significance in preadipocyte cell lines requires further studies of rapid nuclear events following T3 receptor occupancy.
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PMID:Triiodothyronine (T3)-induced down-regulation of the nuclear T3 receptor in mouse preadipocyte cell lines. 376 73

ob gene regulation is as yet unknown. We first examined whether the ob gene is under physiological control by the nutritional state. Fasting produced a sharp (95%) decrease of ob mRNA in epididymal and inguinal fat pads from 24 h onward. Refeeding rapidly (3-6 h) re-induced ob gene expression and corrected it within 24 h. Similar changes in fatty acid synthase (FAS) and GLUT4 mRNAs were observed, whereas phosphoenolpyruvate carboxykinase (PEPCK) mRNA showed an opposite evolution. We next examined the potential role of insulin. In adipose tissue of streptozotocin-diabetic rats, ob mRNA levels were decreased by 80%. Insulin treatment (4 days) only marginally increased ob mRNA, but restored euglycemia and overcorrected FAS, GLUT4 and PEPCK expression. In conclusion, we provide evidence for a physiological regulation of ob gene by variations in the nutritional state. We also show that ob expression is impaired in streptozotocin-diabetic rats and only slightly restored by insulin treatment, which suggests that ob gene is not or only minimally regulated by the hormone.
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PMID:Diet- and diabetes-induced changes of ob gene expression in rat adipose tissue. 755 21

In the present study, we report the long-term metabolic consequences of feeding a milk substitute formula that is high in carbohydrate-derived calories during the suckling period. Male Sprague-Dawley rat pups were raised by gastrostomy on a high carbohydrate (HC) formula or a high fat (HF) formula (which mimicked rat milk composition in macronutrients) during the pre-weaning period (day 4 to 24). These rats were then weaned to a laboratory stock diet and subsequently challenged with a high sucrose diet to augment the development of obesity. The pups receiving the HC formula developed obesity in later life, even though there was no change in the body weight of this group compared to mother-fed (MF) controls or HF formula fed animals during the pre-weaning period. The HC rats were hyperinsulinemic and their growth rates were greater than MF rats starting at day 55. The lipogenic capacity of liver as well as adipose tissues (epididymal and omental) was higher in HC animals compared to MF control animals, as reflected by increases in two key lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase) and in vitro synthesis of lipids. An analysis of adipose tissue morphology in adult rats showed an increase in cell size in epididymal adipose tissue of HC rats compared to the MF group. However, there was no significant difference in cell size in omental adipose tissue between the MF and HC rats. The HF group behaved similarly to the MF control group in growth pattern and measured metabolic parameters.
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PMID:Long-term effects of feeding high carbohydrate diet in pre-weaning period by gastrostomy: a new rat model for obesity. 822 Jun 51

We have previously shown that the effects of a high carbohydrate, fat-free diet and 24-h starvation on fatty acid synthesis in rats are tissue specific. In the present study we examine the tissue-specific pretranslational effects of high carbohydrate feeding, starvation and refeeding a high carbohydrate diet after starvation on the lipogenic pathway by measuring the levels of mRNA encoding acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) using Northern analysis. Additionally, we measured mRNA S14, a sequence tightly associated with lipogenesis. In rats fed the high carbohydrate diet, hepatic levels of the three mRNA were 3-5 fold higher than in controls. The level of S14 mRNA was doubled in epididymal fat, but other effects of this diet in adipose tissues were not significant. Expression in kidney, heart, lung and brain was not altered. Starvation significantly reduced the level of these mRNA in all tissues examined except brain. In liver, refeeding the high carbohydrate diet induced the expression of ACC, FAS and S14 mRNA 20-30 fold compared with the values found in 48-h starved animals. Hyperinduction of ACC and FAS, but not S14 mRNA expression was also observed in adipose tissues. The tissue-specific nature of these effects is consistent with previous measurements of fatty acid synthesis and confirm that this regulation occurs at the pretranslational level.
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PMID:High carbohydrate diet and starvation regulate lipogenic mRNA in rats in a tissue-specific manner. 859 45

The time courses of gene expression, and the nutritional regulation of gene expression of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, malic enzyme, and glucose-6-phosphate dehydrogenase) in epididymal adipose tissue after refeeding food-deprived rats have been investigated and compared with those in liver (previously reported). The mRNA concentrations of lipogenic enzymes reached maximum levels at 24 h after the refeeding in adipose tissue and at 8-16 h in liver, while the enzyme induction reached maximum at 48-72 h in both tissues. Moreover, the mRNAs were more strongly induced in adipose tissue than in liver, whereas the enzyme induction (except malic enzyme) was lower. In adipose tissue of rats fed a carbohydrate diet without protein, the mRNA concentrations of acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, and fatty acid synthase reached comparable levels to those of the carbohydrate/protein diet group. The protein feeding increased the enzyme induction in adipose tissue. As regards reduction of gene expression, lipogenic enzyme mRNA concentrations were not so markedly reduced by starvation or polyunsaturated fatty acids in adipose tissue as in liver. The differences in regulation of lipogenic enzyme gene expression and induction between adipose tissue and liver can be ascribed to tissue specificity.
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PMID:Nutritional regulation of lipogenic enzyme gene expression in rat epididymal adipose tissue. 888 6

The ob gene encodes leptin, a hormone which induces satiety and increases energy expenditure. The peroxisome proliferator-activated receptor gamma 2 isoform (PPAR gamma 2) gene encodes a transcription factor which controls adipocyte differentiation and expression of fat-specific genes. We have studied the regulation of these two genes in white adipose tissue (WAT) during the suckling-weaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight barely varied during the last week of suckling. ob mRNA levels, which were very low in 15-day-old rats, rose approximately 6-fold until weaning at 21 days. When the rats were weaned on to a standard (high-carbohydrate) laboratory chow, epididymal WAT enlarged approximately 7-fold, and ob mRNA kept increasing progressively and doubled between 21 and 30 days. This evolution contrasted with that of fatty acid synthase (FAS) mRNA, which increased sharply, but only after weaning. To distinguish between the influence of developmental and nutritional factors on ob expression, a group of rats was weaned on to a high-fat diet. This prevented the rise in glycaemia and insulinaemia and the decrease in plasma non-esterified fatty acids which otherwise occurred at weaning. This also resulted in a slight (10-15%) decrease in food intake and body weight gain. Under this high-fat diet, the rise of ob mRNA in WAT was augmented (3.7-fold in 30- versus 21-day-old pups), whereas the normal rise in FAS mRNA levels was attenuated. Fat-pad weights and adipocyte cell size and number were roughly similar in high-carbohydrate- and high-fat-weaned pups. mRNA levels of PPAR gamma 2, like those of ob, were low in the WAT of 15-day-old suckling pups, doubled at 21 days, and reached a maximum as soon as 23 days. This evolution further differed from that of ob mRNA in not being influenced by diet composition. In conclusion, ob expression markedly increases during the suckling-weaning transition, and this effect is accentuated by a high-fat diet. Qualitative nutritional changes in ob mRNA were correlated with neither acute changes in adipose-tissue mass, nor cell size/number, nor variations in insulinaemia. PPAR gamma 2 also increased during suckling, but rapidly reached a plateau after weaning and no longer changed thereafter. Unlike ob, PPAR gamma 2 was not influenced by the diet composition.
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PMID:Developmental and nutritional changes of ob and PPAR gamma 2 gene expression in rat white adipose tissue. 902 Aug 80

The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.
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PMID:A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats. 980 37

The mRNAs encoding mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mtHMG-CoA synthase), the rate limiting enzyme in ketone body production, are highly expressed in subcutaneous (SC) and, to a lesser extent, in peri-epididymal (PE) rat adipose tissues. This atypical mtHMG-CoA synthase gene expression is dependent on the age (from 9 weeks of age) and sex (higher in male than in female) of the rats. In contrast, the expression of mtHMG-CoA synthase in SC adipose deposit is independent of the nutritional state (fed versus starved) or of the thermic environment (24 degrees C versus 4 degrees C). The expression of mtHMG-CoA synthase is suppressed in SC fat pads of castrated male rats whereas treatment of castrated rats with testosterone restores a normal level of expression. Moreover, testosterone injection induces the expression mtHMG-CoA synthase in SC adipose tissue of age-matched females. The presence of the mtHMG-CoA synthase immunoreactive protein confers to mitochondria isolated from SC adipose deposits, the capacity to produce ketone bodies at a rate similar to that found in liver mitochondria (SC = 13.7 +/- 0.7, liver = 16.4 +/- 1.4 nmol/min/mg prot). mtHMG-CoA synthase is expressed in the stromal vascular fraction (SVF) whatever the adipose deposit considered. While acetyl-CoA carboxylase (ACC) is only expressed in mature adipocytes, the other lipogenic enzymes, fatty acid synthase (FAS) and citrate cleavage enzyme (CCE), are expressed both in SVF cells and mature adipocytes. The expression of lipogenic enzyme genes is markedly reduced in adipocytes but not in SVF cells isolated from 48-h starved male rats. When SVF is subfractionated, mtHMG-CoA synthase mRNAs are mainly recovered in two fractions containing poorly digested structures such as microcapillaries whereas the lowest expression is found in the pre-adipocyte fraction. Interestingly, FAS and CCE mRNAs co-segregate with mtHMG-CoA synthase mRNA. The possible physiological relevance of such atypical expression of mtHMG-CoA synthase is discussed.
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PMID:Atypical expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in subcutaneous adipose tissue of male rats. 1035 39


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