scholarly journals Evidence for the Regulatory Role of Lipocalin 2 in High-Fat Diet-Induced Adipose Tissue Remodeling in Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3525-3538 ◽  
Author(s):  
Hong Guo ◽  
Merlijn Bazuine ◽  
Daozhong Jin ◽  
Merry M. Huang ◽  
Samuel W. Cushman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Tissue Remodeling ◽  
Peroxisome Proliferator ◽  
Lipocalin 2 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipose Tissue Remodeling ◽  
Fat Depot

Lipocalin 2 (Lcn2) has previously been characterized as an adipokine/cytokine playing a role in glucose and lipid homeostasis. In this study, we investigate the role of Lcn2 in adipose tissue remodeling during high-fat diet (HFD)-induced obesity. We find that Lcn2 protein is highly abundant selectively in inguinal adipose tissue. During 16 weeks of HFD feeding, the inguinal fat depot expanded continuously, whereas the expansion of the epididymal fat depot was reduced in both wild-type (WT) and Lcn2−/− mice. Interestingly, the depot-specific effect of HFD on fat mass was exacerbated and appeared more pronounced and faster in Lcn2−/− mice than in WT mice. In Lcn2−/− mice, adipocyte hypertrophy in both inguinal and epididymal adipose tissue was more profoundly induced by age and HFD when compared with WT mice. The expression of peroxisome proliferator-activated receptor-γ protein was significantly down-regulated, whereas the gene expression of extracellular matrix proteins was up-regulated selectively in epididymal adipocytes of Lcn2−/− mice. Consistent with these observations, collagen deposition was selectively higher in the epididymal, but not in the inguinal adipose depot of Lcn2−/− mice. Administration of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (Rosi) restored adipogenic gene expression. However, Lcn2 deficiency did not alter the responsiveness of adipose tissue to Rosi effects on the extracellular matrix expression. Rosi treatment led to the further enlargement of adipocytes with improved metabolic activity in Lcn2−/− mice, which may be associated with a more pronounced effect of Rosi treatment in reducing TGF-β in Lcn2−/− adipose tissue. Consistent with these in vivo observations, Lcn2 deficiency reduces the adipocyte differentiation capacity of stromal-vascular cells isolated from HFD-fed mice in these cells. Herein Rosi treatment was again able to stimulate adipocyte differentiation to a similar extent in WT and Lcn2−/− inguinal and epididymal stromal-vascular cells. Thus, combined, our data indicate that Lcn2 has a depot-specific role in HFD-induced adipose tissue remodeling.

scholarly journals Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Fen Xu ◽  
David Burk ◽  
Zhanguo Gao ◽  
Jun Yin ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Nuclear Factor Κb ◽  
The Body ◽  
Sirtuin 1 ◽  
Vascular Density ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.

scholarly journals Cyclin G2 Regulates Adipogenesis through PPARγ Coactivation

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5247-5254 ◽  
Author(s):  
Victor Aguilar ◽  
Jean-Sébastien Annicotte ◽  
Xavier Escote ◽  
Joan Vendrell ◽  
Dominique Langin ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Luciferase Reporter ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Cell Cycle Regulators ◽  
Luciferase Reporter Gene ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cyclin G2 ◽  
Regulatory Effects

Cell cycle regulators such as cyclins, cyclin-dependent kinases, or retinoblastoma protein play important roles in the differentiation of adipocytes. In the present paper, we investigated the role of cyclin G2 as a positive regulator of adipogenesis. Cyclin G2 is an unconventional cyclin which expression is up-regulated during growth inhibition or apoptosis. Using the 3T3-F442A cell line, we observed an up-regulation of cyclin G2 expression at protein and mRNA levels throughout the process of cell differentiation, with a further induction of adipogenesis when the protein is transiently overexpressed. We show here that the positive regulatory effects of cyclin G2 in adipocyte differentiation are mediated by direct binding of cyclin G2 to peroxisome proliferator-activated receptor γ (PPARγ), the key regulator of adipocyte differentiation. The role of cyclin G2 as a novel PPARγ coactivator was further demonstrated by chromatin immunoprecipitation assays, which showed that the protein is present in the PPARγ-responsive element of the promoter of aP2, which is a PPARγ target gene. Luciferase reporter gene assays, showed that cyclin G2 positively regulates the transcriptional activity of PPARγ. The role of cyclin G2 in adipogenesis is further underscored by its increased expression in mice fed a high-fat diet. Taken together, our results demonstrate a novel role for cyclin G2 in the regulation of adipogenesis.

scholarly journals INDUCTION OF BROWN ADIPOSE TISSUE: A REVIEW

2018 ◽  
Vol 11 (5) ◽  
pp. 472
Author(s):  
Ivo Romauld Sagayaraj ◽  
Akilashree S ◽  
Brindha Devi P
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Secreted Proteins ◽  
Peroxisome Proliferator ◽  
Basic Study ◽  
Peroxisome Proliferator Activated Receptor ◽  
Efficient Treatment ◽  
Major Health ◽  
Brown Adipose

Objective: Obesity is the major problem which may lead to many other health ailments such as atherosclerosis, stroke, and depression. Both the cause as well as the treatment lies in the adipose tissue. The two main adipocytes, white adipose tissue (WAT) and brown adipose tissue (BAT) are responsible for the accumulation of fat and transformation of fat into heat, respectively. This review discusses the induction of BAT and browning of WAT by different pathways and activators to decrease the rate of obesity. Methods: Understanding the regulators, activators and secreted proteins which induce browning of WAT to BAT, as the BAT engage in thermogenesis process and transform fat into heat rather than storing it (WAT). Some of the core regulators are peroxisome proliferator-activated receptor-γ, PRDM16, PGC-1α. Results: A basic study explained about the origin of BAT and its functions, the function of hormones in BAT growth and its regulations. These studies provided the platform to understand about the mechanism of regulators, activators and secreted proteins which help in treating obesity and its related disorders by inducing the amount of BAT. Conclusion: The major health ailments caused by obesity can be reduced by increasing the activity of BAT and transforming WAT into BAT. A challenging way to treat these ailments is by regulating the activators and hormones responsible for the induction of BAT, so it transforms the excess fat into heat and avoiding the accumulation of fat. By understanding the role of regulators in the adipose tissue can provide various methods to reduce the chance of obesity and enhance efficient treatment in both children and adults.

Role of intracellular calcium in human adipocyte differentiation

2000 ◽  
Vol 3 (2) ◽  
pp. 75-82 ◽  
Author(s):  
HANG SHI ◽  
YUAN-DI HALVORSEN ◽  
PAMELA N. ELLIS ◽  
WILLIAM O. WILKISON ◽  
MICHAEL B. ZEMEL
Keyword(s):  
Intracellular Calcium ◽  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Adipocyte ◽  
Gpdh Activity ◽  
Early Stages ◽  
Triglyceride Accumulation ◽  
Mild Stimulation

Shi, Hang, Yuan-Di Halvorsen, Pamela N. Ellis, William O. Wilkison, and Michael B. Zemel. Role of intracellular calcium in human adipocyte differentiation. Physiol Genomics 3: 75–82, 2000.—Intracellular calcium ([Ca2+]i) modulates adipocyte lipid metabolism and inhibits the early stages of murine adipogenesis. Consequently, we evaluated effects of increasing [Ca2+]i in early and late stages of human adipocyte differentiation. Increasing [Ca2+]i with either thapsigargin or A23187 at 0–1 h of differentiation markedly suppressed differentiation, with a 40–70% decrease in triglyceride accumulation and glycerol-3 phosphate dehydrogenase (GPDH) activity ( P < 0.005). However, a 1-h pulse of either agent at 47–48 h only modestly inhibited differentiation. Sustained, mild stimulation of Ca2+ influx with either agouti protein or 10 mM KCl-induced depolarization during 0–48 h of differentiation inhibited triglyceride accumulation and GPDH activity by 20–70% ( P < 0.05) and markedly suppressed peroxisome proliferator-activated receptor gamma (PPARγ) expression. These effects were reversed by Ca2+ channel antagonism. In contrast, Ca2+ pulses late in differentiation (71–72 h or 48–72 h) markedly increased these markers of differentiation. Thus increasing [Ca2+]i appears to exert a biphasic regulatory role in human adipocyte differentiation, inhibiting the early stages while promoting the late stage of differentiation and lipid filling.

scholarly journals Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 26 ◽  
Author(s):  
Jin Choi ◽  
No-Joon Song ◽  
A Lee ◽  
Dong Lee ◽  
Min-Ju Seo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Obese Mice ◽  
High Fat ◽  
White Adipocyte

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.

scholarly journals Lipocalin 2 regulates retinoic acid-induced activation of beige adipocytes

2018 ◽  
Vol 61 (3) ◽  
pp. 115-126 ◽  
Author(s):  
Jessica A Deis ◽  
Hong Guo ◽  
Yingjie Wu ◽  
Chengyu Liu ◽  
David A Bernlohr ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Retinoic Acid ◽  
Uncoupling Protein ◽  
Oxidative Capacity ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Lipocalin 2 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Beige Adipocytes

Lipocalin-2 (LCN2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for LCN2 in the recruitment and retinoic acid-induced activation of brown-like or ‘beige’ adipocytes. We found LCN2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived from Lcn2 −/− mice. Lcn2 −/− inguinal adipocytes have attenuated insulin-induced upregulation of thermogenic gene expression and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway activation. This is accompanied by a lower basal and maximal oxidative capacity in Lcn2 −/− inguinal adipocytes, indicating mitochondrial dysfunction. Recombinant Lcn2 was able to restore insulin-induced p38MAPK phosphorylation in both WT and Lcn2 −/− inguinal adipocytes. Rosiglitazone treatment during differentiation of Lcn2 −/− adipocytes is able to recruit beige adipocytes at a normal level, however, further activation of beige adipocytes by insulin and RA is impaired in the absence of LCN2. Further, the synergistic effect of insulin and RA on UCP1 and PGC-1α expression is markedly reduced in Lcn2 −/− inguinal adipocytes. Most intriguingly, LCN2 and the retinoic acid receptor-alpha (RAR-α) are concurrently translocated to the plasma membrane of adipocytes in response to insulin, and this insulin-induced RAR-α translocation is absent in adipocytes deficient in LCN2. Our data suggest a novel LCN2-mediated pathway by which RA and insulin synergistically regulates activation of beige adipocytes via a non-genomic pathway of RA action.

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