Regulation of obese gene expression in KK mice and congenic lethal yellow obese KKAy mice

1996 ◽  
Vol 271 (2) ◽  
pp. E333-E339 ◽  
Author(s):  
M. Hayase ◽  
Y. Ogawa ◽  
G. Katsuura ◽  
H. Shintaku ◽  
K. Hosoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Tissue Expression ◽  
Mouse Strains ◽  
Mrna Levels ◽  
Ob Gene ◽  
Kk Mice ◽  
Kkay Mice ◽  
Obesity And Diabetes ◽  
Lethal Yellow

To elucidate the regulation of obese (ob) gene expression in obesity and diabetes, we examined ob gene expression in KK mice and congenic lethal yellow obese KKAy mice. Northern blot analysis revealed that the ob mRNA levels are roughly equivalent in each of the epididymal, mesenteric, and subcutaneous white adipose tissue (WAT) from KK and KKAy mice at 4 wk of age, when the obese phenotype of KKAy mice was not apparent. Expression of the ob gene was augmented in the mesenteric and subcutaneous WAT but was unchanged in the epididymal WAT in KKAy mice at 12 wk of age, when KKAy mice developed marked obesity with hyperglycemia, hyperlipidemia, and hyperinsulinemia. The ob gene expression was also examined during fasting in 12-wk-old KK and KKAy mice. After 24 or 72 h of fasting in both mouse strains, ob gene expression was downregulated in the epididymal and mesenteric WAT but was unchanged in the subcutaneous WAT. The present study demonstrates that adipose tissue expression of the ob gene is regulated depending on the nutritional status in KK and KKAy mice.

scholarly journals Insulin and insulin-like growth factor 1 antagonize the stimulation of ob gene expression by dexamethasone in cultured rat adipose tissue

1997 ◽  
Vol 324 (2) ◽  
pp. 605-610 ◽  
Author(s):  
Bénédicte A. REUL ◽  
Lumbe N. ONGEMBA ◽  
Anne-Marie Marie ◽  
Jean-Claude HENQUIN ◽  
Sonia M. BRICHARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Fatty Acid Synthase ◽  
Glucose Transporter ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Ob Gene ◽  
Rat Adipose Tissue

The ob gene, specifically expressed in fat cells, encodes leptin, a hormone that induces satiety and increases energy expenditure. In this study, we investigated the interactions between glucocorticoids and insulin on ob gene expression in cultured explants of rat adipose tissue. Only low levels of ob mRNA were detected when adipose tissue from fasted rats was cultured for 12–24 h in minimal essential medium. However, the addition of dexamethasone to the medium increased ob gene expression in a concentration-dependent manner (EC50 10 nM). With 1 μM dexamethasone, ob mRNA levels were similar to those in fresh fat pads from fed rats, reaching a maximum after 12 h. The effect of dexamethasone was blocked by actinomycin D, which indicates an action on transcription. This effect was increased when a minimum amount of fuel (glucose or a mixture of lactate and pyruvate) was supplied in the medium. Unlike dexamethasone, insulin, even when combined with high glucose concentrations, did not induce ob expression, although it strongly increased the accumulation of mRNA species for fatty acid synthase (FAS), the insulin-sensitive glucose transporter GLUT4 and the γ isoform of peroxisome proliferator-activated receptor (PPARγ). Unexpectedly, insulin dose-dependently inhibited dexamethasone-induced ob mRNA accumulation. This effect was observed at low concentrations of insulin (IC50 1 nM) and was delayed in onset, beginning after 6–9 h of culture. It was mimicked by insulin-like growth factor 1 (IGF-1) (100 nM). The inhibition by insulin was only detectable when fuels were present and/or when a critical level of ob expression was reached. As this inhibitory effect was reversed by cycloheximide, this suggests that it required ongoing protein synthesis. In conclusion, unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression. On the other hand, insulin (and IGF-1) even inhibited the dexamethasone-induced accumulation of ob mRNA. The underlying mechanism involved ongoing synthesis of an inhibitory protein by insulin, which is in keeping with its delayed effect. Moreover, the expression of genes for FAS, GLUT4 and PPARγ may be inversely related to that of ob.

Metallothionein gene expression and secretion in white adipose tissue

2000 ◽  
Vol 279 (6) ◽  
pp. R2329-R2335 ◽  
Author(s):  
Paul Trayhurn ◽  
Jacqueline S. Duncan ◽  
Anne M. Wood ◽  
John H. Beattie
Keyword(s):  
Gene Expression ◽  
Molecular Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Low Molecular Weight ◽  
Secretory Product ◽  
Mrna Levels ◽  
Gene Encoding ◽  
Adrenoceptor Agonist

White adipose tissue (WAT) has been examined to determine whether the gene encoding metallothionein (MT), a low-molecular-weight stress response protein, is expressed in the tissue and whether MT may be a secretory product of adipocytes. The MT-1 gene was expressed in epididymal WAT, with MT-1 mRNA levels being similar in lean and obese ( ob/ ob) mice. MT-1 mRNA was found in each of the main adipose tissue sites (epididymal, perirenal, omental, subcutaneous), and there was no major difference between depots. Separation of adipocytes from the stromal-vascular fraction of WAT indicated that the MT gene (MT-1 and MT-2) was expressed in adipocytes themselves. Treatment of mice with zinc had no effect on MT-1 mRNA levels in WAT, despite strong induction of MT-1 expression in the liver. MT-1 gene expression in WAT was also unaltered by fasting or norepinephrine. However, administration of a β3-adrenoceptor agonist, BRL-35153A, led to a significant increase in MT-1 mRNA. On differentiation of fibroblastic preadipocytes to adipocytes in primary culture, MT was detected in the medium, suggesting that the protein may be secreted from WAT. It is concluded that WAT may be a significant site of MT production; within adipocytes, MT could play an antioxidant role in protecting fatty acids from damage.

scholarly journals Lack of adipose-specific hexose-6-phosphate dehydrogenase causes inactivation of adipose glucocorticoids and improves metabolic phenotype in mice

2019 ◽  
Vol 133 (21) ◽  
pp. 2189-2202
Author(s):  
Jian Wang ◽  
Ying Wang ◽  
Limei Liu ◽  
Kabirullah Lutfy ◽  
Theodore C. Friedman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fasting Blood Glucose ◽  
Visceral Obesity ◽  
Conditional Knockout ◽  
Hormone Sensitive Lipase ◽  
Metabolic Phenotype ◽  
Mrna Levels ◽  
Obesity And Diabetes ◽  
Factor C

Abstract Excessive glucocorticoid (GC) production in adipose tissue promotes the development of visceral obesity and metabolic syndrome (MS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is critical for controlling intracellular GC production, and this process is tightly regulated by hexose-6-phosphate dehydrogenase (H6PDH). To better understand the integrated molecular physiological effects of adipose H6PDH, we created a tissue-specific knockout of the H6PDH gene mouse model in adipocytes (adipocyte-specific conditional knockout of H6PDH (H6PDHAcKO) mice). H6PDHAcKO mice exhibited almost complete absence of H6PDH expression and decreased intra-adipose corticosterone production with a reduction in 11β-HSD1 activity in adipose tissue. These mice also had decreased abdominal fat mass, which was paralleled by decreased adipose lipogenic acetyl-CoA carboxylase (ACC) and ATP-citrate lyase (ACL) gene expression and reduction in their transcription factor C/EBPα mRNA levels. Moreover, H6PDHAcKO mice also had reduced fasting blood glucose levels, increased glucose tolerance, and increased insulin sensitivity. In addition, plasma free fatty acid (FFA) levels were decreased with a concomitant decrease in the expression of lipase adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in adipose tissue. These results indicate that inactivation of adipocyte H6PDH expression is sufficient to cause intra-adipose GC inactivation that leads to a favorable pattern of metabolic phenotypes. These data suggest that H6PDHAcKO mice may provide a good model for studying the potential contributions of fat-specific H6PDH inhibition to improve the metabolic phenotype in vivo. Our study suggests that suppression or inactivation of H6PDH expression in adipocytes could be an effective intervention for treating obesity and diabetes.

Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue

1997 ◽  
Vol 273 (2) ◽  
pp. R762-R767 ◽  
Author(s):  
A. Chaudhry ◽  
J. G. Granneman
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adenylyl Cyclase ◽  
Regulation Of Gene Expression ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Functional Responses ◽  
Synergistic Interactions ◽  
Brown Adipose

Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.

scholarly journals Adipose Tissue Expansion by Overfeeding Healthy Men Alters Iron Gene Expression

2018 ◽  
Vol 104 (3) ◽  
pp. 688-696 ◽  
Author(s):  
Berenice Segrestin ◽  
José Maria Moreno-Navarrete ◽  
Kevin Seyssel ◽  
Maud Alligier ◽  
Emmanuelle Meugnier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Serum Iron ◽  
Tissue Expansion ◽  
Lipid Storage ◽  
Mrna Levels ◽  
Intracellular Iron ◽  
Gene Encoding ◽  
Iron Storage ◽  
Healthy Men

Abstract Context Iron overload has been associated with greater adipose tissue (AT) depots. We retrospectively studied the potential interactions between iron and AT during an experimental overfeeding in participants without obesity. Methods Twenty-six participants (mean body mass index ± SD, 24.7 ± 3.1 kg/m2) underwent a 56-day overfeeding (+760 kcal/d). Serum iron biomarkers (ELISA), subcutaneous AT (SAT) gene expression, and abdominal AT distribution assessed by MRI were analyzed at the beginning and the end of the intervention. Results Before intervention: SAT mRNA expression of the iron transporter transferrin (Tf) was positively correlated with the expression of genes related to lipogenesis (lipin 1, ACSL1) and lipid storage (SCD). SAT expression of the ferritin light chain (FTL) gene, encoding ferritin (FT), an intracellular iron storage protein, was negatively correlated to SREBF1, a gene related to lipogenesis. Serum FT (mean, 92 ± 57 ng/mL) was negatively correlated with the expression of SAT genes linked to lipid storage (SCD, DGAT2) and to lipogenesis (SREBF1, ACSL1). After intervention: Overfeeding led to a 2.3 ± 1.3-kg weight gain. In parallel to increased expression of lipid storage–related genes (mitoNEET, SCD, DGAT2, SREBF1), SAT Tf, SLC40A1 (encoding ferroportin 1, a membrane iron export channel) and hephaestin mRNA levels increased, whereas SAT FTL mRNA decreased, suggesting increased AT iron requirement. Serum FT decreased to 67 ± 43 ng/mL. However, no significant associations between serum iron biomarkers and AT distribution or expansion were observed. Conclusion In healthy men, iron metabolism gene expression in SAT is associated with lipid storage and lipogenesis genes expression and is modulated during a 56-day overfeeding diet.

scholarly journals Regulation of GLUT4 gene expression by SREBP-1c in adipocytes

2006 ◽  
Vol 399 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Seung-Soon Im ◽  
Sool-Ki Kwon ◽  
Seung-Youn Kang ◽  
Tae-Hyun Kim ◽  
Ha-Il Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Glucose Transporter ◽  
Regulatory Element ◽  
Diabetic Rats ◽  
Dominant Negative ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Response Element ◽  
Glut4 Gene Expression

Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is subject to hormonal or metabolic control. In the present study, we have characterized an adipose tissue transcription factor that is influenced by fasting/refeeding regimens and insulin. Northern blotting showed that refeeding increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-element-binding protein)-1c in adipose tissue were also increased by refeeding. In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and electrophoretic mobility-shift assay studies indicated that the putative sterol response element is located in the region between bases −109 and −100 of the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4, suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the putative sterol-response element in the GLUT4. Furthermore, treating streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In addition, we have identified an Sp1 binding site adjacent to the functional sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in adipose tissue.

scholarly journals Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice

2007 ◽  
Vol 292 (4) ◽  
pp. E1101-E1109 ◽  
Author(s):  
S. M. Turner ◽  
S. Roy ◽  
H. S. Sul ◽  
R. A. Neese ◽  
E. J. Murphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Adipose Tissue ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression ◽  
Leptin Deficiency ◽  
Normal Expression

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using 2H2O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 μg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.

scholarly journals Postnatal selective suppression of lipoprotein lipase gene expression in brown adipose tissue (relative to the expression of the gene for the uncoupling protein) is not due to adrenergic insensitivity: a possible specific inhibitory effect of colostrum

1996 ◽  
Vol 314 (1) ◽  
pp. 261-267 ◽  
Author(s):  
María-Jesus OBREGÓN ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Selective Suppression ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Lpl Gene

The levels of mRNA coding for the uncoupling protein (UCP) and for lipoprotein lipase (LPL) were monitored in the brown adipose tissue of newborn rat pups. At 5 h after birth, the mRNA levels of UCP and LPL were high in pups exposed singly to 28 °C and low in pups kept singly at thermoneutrality (36 °C); in pups staying with the dam, the UCP mRNA levels were intermediate. However, the LPL mRNA levels were lower in pups staying with the dam than in pups at 36 °C, implying that factors additional to environmental temperature influenced LPL gene expression. Injection of noradrenaline into pups at thermoneutrality (36 °C) led to increases in UCP and LPL gene expression, but noradrenaline injections had no further effect in cold-exposed pups. The adrenergic effects were mediated via β-adrenergic receptors. The cold-induced increases in both UCP and LPL gene expression were abolished by the β-adrenergic antagonist propranolol. Thus differences in adrenergic responsiveness could not explain the differential expression of the UCP and LPL genes observed in pups staying with the dam. The presence of a physiological suppressor was examined by feeding single pups at 28 °C with different foods: nothing, water, Intralipid, cow's milk, rat milk and rat colostrum. None of these agents led to suppression of UCP gene expression, but colostrum led to a selective suppression of LPL gene expression. It was concluded that the genes for UCP and LPL were responsive to adrenergic stimuli immediately after birth, and it is suggested that a component of rat colostrum can selectively suppress LPL gene expression.

scholarly journals Comparison of leptin gene expression in different adipose tissues in children and adults

2004 ◽  
pp. 579-584 ◽  
Author(s):  
E Schoof ◽  
A Stuppy ◽  
F Harig ◽  
R Carbon ◽  
T Horbach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Subcutaneous Tissue ◽  
Mrna Levels ◽  
Adipose Tissues ◽  
Metabolic Properties ◽  
Tissue Specimens ◽  
Plasma Leptin ◽  
Design And Methods

OBJECTIVE: Adipose tissue displays depot-specific metabolic properties and a predominant gene expression of leptin in subcutaneous tissue. The aim of the study was to evaluate leptin mRNA expression in various adipose tissues and to relate it to plasma leptin concentrations. Furthermore, developmental changes in leptin gene expression from childhood to adulthood were examined. DESIGN AND METHODS: Thoracic subcutaneous and intrathoracic adipose tissue specimens were obtained in 22 adults (51-81 years) and 23 children (0.1-17 years) undergoing cardiac surgery, and abdominal subcutaneous, omental and mesenterial fat specimens were collected from 21 adults (38-79 years) and 22 children (0.2-17 years) before abdominal surgery. Preoperative plasma leptin concentrations were measured by RIA. Leptin mRNA expression was quantified by TaqMan real-time PCR. RESULTS: In adults, there was no difference between leptin gene expression in subcutaneous and intrathoracic fat, whereas in children leptin mRNA expression was significantly higher in subcutaneous adipose tissue. In omental fat, leptin mRNA levels were significantly lower compared with subcutaneous and mesenterial sites in both children and adults. Adults revealed a significantly higher leptin gene expression in subcutaneous, omental and mesenterial adipose tissues than children. Subcutaneous and omental leptin gene expression are independent factors for plasma leptin concentrations in children and adults. CONCLUSION: Leptin is differentially expressed at different adipose tissue sites, a situation which is even more pronounced in children. There is a developmental increase in leptin mRNA expression in adipose tissue during childhood, reaching maximal capacity in adulthood.

scholarly journals Circulating leptin during ovine pregnancy in relation to maternal nutrition, body composition and pregnancy outcome

2001 ◽  
Vol 169 (3) ◽  
pp. 465-476 ◽  
Author(s):  
L Thomas ◽  
JM Wallace ◽  
RP Aitken ◽  
JG Mercer ◽  
P Trayhurn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Composition ◽  
Adipose Tissue ◽  
Dietary Intake ◽  
Leptin Receptor ◽  
Maternal Nutrition ◽  
Receptor Gene ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Receptor Gene Expression

This study examined the pattern of circulating leptin in age-matched sheep during adolescent pregnancy, and its relationship with maternal dietary intake, body composition and tissue expression of the leptin gene. Overfeeding the adolescent pregnant ewe results in rapid maternal growth at the expense of the placenta, leading to growth restriction in the fetus, compared with normal fed controls. Our results demonstrate that, in the adolescent ewe, overfeeding throughout pregnancy was associated with higher maternal leptin concentrations, when compared with moderately fed controls (P<0.05), with no peak in circulating leptin towards the end of pregnancy. There was a close correlation between indices of body composition and circulating leptin levels at day 104 of gestation and at term (P<0.03). Further, when the dietary intake was switched from moderate to high, or high to moderate, at day 50 of gestation, circulating leptin levels changed rapidly, in parallel with the changes in dietary intake. Leptin mRNA levels and leptin protein in perirenal adipose tissue samples, taken at day 128 of gestation, were higher in overfed dams (P<0.04), suggesting that adipose tissue was the source of the increase in circulating leptin in the overnourished ewes. Leptin protein was also detected in placenta but leptin gene expression was negligible. However, leptin receptor gene expression was detected in the ovine placenta, suggesting that the placenta is a target organ for leptin. A negative association existed between maternal circulating leptin and fetal birth weight, placental/cotyledon weight and cotyledon number. In conclusion, in this particular ovine model, hyperleptinaemia was not observed during late pregnancy. Instead, circulating leptin concentrations reflected increased levels of leptin secretion by adipose tissue primarily as a result of the increase in body fat deposition, due to overfeeding. However, there appears to be a direct effect of overfeeding, particularly in the short term. In the nutritional switch-over study, circulating leptin concentrations changed within 48 h of the change in dietary intake. The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and/or fetal development.

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