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.

Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O

2004 ◽  
Vol 286 (4) ◽  
pp. E577-E588 ◽  
Author(s):  
A. Strawford ◽  
F. Antelo ◽  
M. Christiansen ◽  
M. K. Hellerstein
Keyword(s):  
Cell Proliferation ◽  
Adipose Tissue ◽  
Half Life ◽  
De Novo ◽  
Human Subjects ◽  
De Novo Lipogenesis ◽  
Gas Chromatography Mass Spectrometry ◽  
Distribution Analysis ◽  
Mass Isotopomer Distribution Analysis

The turnover of adipose tissue components (lipids and cells) and the pathways of adipose lipid deposition have been difficult to measure in humans. We apply here a 2H2O long-term labeling technique for concurrent measurement of adipose-triglyceride (TG) turnover, cell (DNA) proliferation, and de novo lipogenesis (DNL). Healthy subjects drank 2H2O (70 ml/day) for 5-9 wk. Subcutaneous adipose tissue aspirates were taken (gluteal, thigh, and flank depots). Deuterium incorporation into TG glycerol (representing all-source TG synthesis), TG palmitate (representing DNL, by mass isotopomer distribution analysis), and DNA (representing cell proliferation) was measured by gas chromatography-mass spectrometry. Subjects tolerated the protocol well, and body 2H2O enrichments were stable. Mean TG-glycerol fractional synthesis was 0.12 (i.e., 12%) with a range of 0.03-0.32 after 5 wk and 0.20 (range 0.08-0.49) after 9 wk (TG half-life 200-270 days). Label decay measurements 5-8 mo after discontinuing 2H2O gave similar turnover estimates. Net lipolysis (TG turnover) was 50-60 g/day. DNL contribution to adipose-TG was 0.04 after 9 wk, representing ∼20% of newly deposited TG. Cell proliferation was 0.10-0.17 after 9 wk (half-life 240-425 days). In summary, long-term 2H2O administration to human subjects allows measurement of the dynamics of adipose tissue components. Turnover of all elements is slow, and DNL contributes ∼20% of new TG.

scholarly journals Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

2018 ◽  
Vol 19 (10) ◽  
pp. 2904 ◽  
Author(s):  
Christian Carpéné ◽  
Saioa Gómez-Zorita ◽  
Alice Chaplin ◽  
Josep Mercader
Keyword(s):  
Adipose Tissue ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Uncoupling Protein ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Brown Adipose ◽  
High Sucrose ◽  
Sucrose Drinking

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

scholarly journals Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 342 ◽  
Author(s):  
Alexandra Marziou ◽  
Clothilde Philouze ◽  
Charlène Couturier ◽  
Julien Astier ◽  
Philippe Obert ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Triglyceride Accumulation

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.

scholarly journals The DAXX-SREBP axis promotes oncogenic lipogenesis and tumorigenesis

2021 ◽  
Author(s):  
Iqbal Mahmud ◽  
Guimei Tian ◽  
Jia Wang ◽  
Jessica Lewis ◽  
Aaron Waddell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
De Novo ◽  
Lipid Synthesis ◽  
De Novo Lipogenesis ◽  
Recent Analysis ◽  
Gene Promoters ◽  
Lipogenic Gene ◽  
Lipogenic Gene Expression ◽  
Cancer Types

ABSTRACTDe novo lipogenesis produces lipids for membrane biosynthesis and cell signaling. Elevated lipogenesis is a major metabolic feature in cancer cells. In breast and other cancer types, genes involved in lipogenesis are highly upregulated, but the mechanisms that control their expression remain poorly understood. DAXX modulates gene expression through binding to diverse transcription factors although the functional impact of these diverse interactions remains to be defined. Our recent analysis indicates that DAXX is overexpressed in diverse cancer types. However, mechanisms underlying DAXX’s oncogenic function remains elusive. Using global integrated transcriptomic and lipidomic analyses, we show that DAXX plays a key role in lipid metabolism. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipid synthesis and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and a DAXX mutant unable to bind SREBPs are incapable of promoting lipogenesis and tumor growth. Our results identify the DAXX-SREBP axis as an important pathway for tumorigenesis.

155 Low Insulin Sensitivity Is Associated with Increased Body Fat and Changes in Gene Expression of Lipogenic Enzymes in the Adipose Tissue of Finishing Pigs

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 83-84
Author(s):  
Hector H Salgado ◽  
Marie-France Palin ◽  
Hélène Lapierre ◽  
Aline Remus ◽  
Marie-Pierre Letourneau-Montminy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Body Fat ◽  
De Novo ◽  
Mrna Abundance ◽  
De Novo Lipogenesis ◽  
Peroxisome Proliferator ◽  
Lipogenic Enzymes ◽  
Glucose Ingestion

Abstract Variations in body fat (BF) among pigs can be associated with differences in insulin sensitivity given the insulin anabolic effect in lipid synthesis. The study objectives were to characterize this association and compare the relative mRNA abundance of genes associated with insulin resistance and de novo lipogenesis in the adipose tissue of fat and lean pigs. Thirty 95 kg pigs, catheterized in the jugular vein, received an oral dose of 1.75 g glucose/kg of BW after 18 hours of fasting. Blood samples were collected at -20, -10, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300 and 360 minutes following glucose ingestion. Insulin sensitivity indexes were calculated and analyzed. The BF (%) was estimated by dual X-ray densitometry. The 8 fattest (22 % BF) and the 8 leanest pigs (17.2 % BF) were used to determine the relative mRNA abundance of studied genes using real-time qPCR analyses. Insulin sensitivity was determined using QUICKI and Matsuda indexes, respectively, and their association with body fat was studied with Spearman correlations. Differences in gene expression and insulin sensitivity between fat and lean pigs were studied with a one-way ANOVA. The QUICKI and Matsuda indexes negatively correlated with BF (r = -0.67 and r = -0.59; P < 0.001). Fat pigs had reduced insulin sensitivity and higher relative mRNA abundance of lipogenic enzymes (ACACA, ACLY, FASN; P < 0.05) than lean pigs. The higher expression level of glucose-6-phosphate dehydrogenase (G6PD) combined with the trend (P < 0.10) of lower expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in fat pigs may explain part of their reduced insulin sensitivity. These results suggest that an increased BF is associated with reduced insulin sensitivity and greater expression of lipogenic enzymes in pig adipose tissue.

scholarly journals Loss of Histone Deacetylase 4 in Hepatocytes Increases De Novo Lipogenesis in Diet-Induced Obesity Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1652-1652
Author(s):  
Yoojin Lee ◽  
Minkyung Bae ◽  
Dana Chamberlain ◽  
Tho Pham ◽  
Hyunju Kang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Histone Deacetylase ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Blood Analysis ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Hepatic Expression ◽  
Histone Deacetylase 4

Abstract Objectives Evidence suggests that histone deacetylase 4 (HDAC4) is downregulated in adipose tissue of obese subjects. We determined the role of HDAC4 in the regulation of energy metabolism of metabolically active tissues, such as the liver and adipose tissue. Methods Hepatocyte-specific (Hdac4HKO) and adipocyte-specific (Hdac4AKO) Hdac4 knockout mice were generated by crossing homozygous Hdac4 floxed (Hdac4fl/fl) mice with mice expressing Cre recombinase under the control of the enhancer/promoter of Albumin or Adipoq gene, respectively. Hdac4fl/fl and Hdac4HKO mice were fed a high fat/high sucrose (HF/HS; 57%/28% energy from fat/sucrose) with 2% cholesterol (w/w) diet for 16 weeks. Hdac4fl/fl and Hdac4AKO mice were fed an obesogenic HF/HS diet for 16 weeks. The final serum was collected by cardiopuncture for blood analysis. Tissues were snap frozen for mRNA and protein analysis. Results Both Hdac4HKO and Hdac4AKO mice did not show differences in body weight compared to Hdac4fl/fl mice following the 16-week of experimental diet. However, loss of hepatic HDAC4 increased serum alanine transaminase levels, a marker for liver injury. Also, Hdac4HKO mice had exacerbated hepatic steatosis with higher liver weights and triglyceride levels than Hdac4fl/fl mice. Consistently, hepatic expression of genes for de novo lipogenesis, including Srebf1c and its target genes, fatty acid synthase and acetyl CoA carboxylase 1, was significantly higher in Hdac4HKO mice compared with control mice. Interestingly, the loss of hepatocyte HDAC4 aggravated inflammation and fibrosis in white adipose tissue. Serum cytokine array indicated increases in fibroblast growth factor 1, pentraxin 3, tissue inhibitor of metalloproteinases 1, and decrease in endocan, which may contribute to the crosstalk between the liver and adipose tissue in Hdac4HKO. On the other hand, the loss of adipocyte HDAC4 elicited minimal changes in mRNA levels of lipogenic, inflammatory, and fibrogenic genes in adipose tissue and the liver. Conclusions The lack of functional hepatocyte HDAC4 increased lipid accumulation in the liver of obesity mice via increasing hepatic de novo lipogenesis, and also aggravated adipose tissue inflammation and fibrosis. Further investigation is warranted to elucidate the crosstalk between the liver and adipose tissue in Hdac4HKO. Funding Sources This study was supported by NIH.

scholarly journals Effect of Central Corticotropin-Releasing Factor on Hepatic Lipid Metabolism and Inflammation-Related Gene Expression in Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 3940
Author(s):  
Yukiomi Nakade ◽  
Rena Kitano ◽  
Taeko Yamauchi ◽  
Satoshi Kimoto ◽  
Kazumasa Sakamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
De Novo ◽  
Corticotropin Releasing Factor ◽  
De Novo Lipogenesis ◽  
Control Group ◽  
Mrna Levels ◽  
Related Gene ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 μg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1β mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1β mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.

Liver X receptors regulate de novo lipogenesis in a tissue-specific manner in C57BL/6 female mice

2011 ◽  
Vol 301 (1) ◽  
pp. E210-E222 ◽  
Author(s):  
Marion Korach-André ◽  
Amena Archer ◽  
Chiara Gabbi ◽  
Rodrigo P. Barros ◽  
Matteo Pedrelli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Glucose Sensor ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Bile Acid Metabolism ◽  
Liver X Receptors ◽  
Tissue Specific ◽  
Specific Regulation ◽  
X Receptors

The liver X receptors (LXRs) play a key role in cholesterol and bile acid metabolism but are also important regulators of glucose metabolism. Recently, LXRs have been proposed as a glucose sensor affecting LXR-dependent gene expression. We challenged wild-type (WT) and LXRαβ−/− mice with a normal diet (ND) or a high-carbohydrate diet (HCD). Magnetic resonance imaging showed different fat distribution between WT and LXRαβ−/− mice. Surprisingly, gonadal (GL) adipocyte volume decreased on HCD compared with ND in WT mice, whereas it slightly increased in LXRαβ−/− mice. Interestingly, insulin-stimulated lipogenesis of isolated GL fat cells was reduced on HCD compared with ND in LXRαβ−/− mice, whereas no changes were observed in WT mice. Net de novo lipogenesis (DNL) calculated from V̇o2 and V̇co2 was significantly higher in LXRαβ−/− than in WT mice on HCD. Histology of HCD-fed livers showed hepatic steatosis in WT mice but not in LXRαβ−/− mice. Glucose tolerance was not different between groups, but insulin sensitivity was decreased by the HCD in WT but not in LXRαβ−/− mice. Finally, gene expression analysis of adipose tissue showed induced expression of genes involved in DNL in LXRαβ−/− mice compared with WT animals as opposed to the liver, where expression of DNL genes was repressed in LXRαβ−/− mice. We thus conclude that absence of LXRs stimulates DNL in adipose tissue, but suppresses DNL in the liver, demonstrating opposite roles of LXR in DNL regulation in these two tissues. These results show tissue-specific regulation of LXR activity, a crucial finding for drug development.

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.

Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue

1987 ◽  
Vol 253 (6) ◽  
pp. E664-E669 ◽  
Author(s):  
C. Chascione ◽  
D. H. Elwyn ◽  
M. Davila ◽  
K. M. Gil ◽  
J. Askanazi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
High Intake ◽  
Carbohydrate Diet ◽  
Triglyceride Synthesis ◽  
High Carbohydrate

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.

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