scholarly journals Cancer cachexia differentially regulates visceral adipose tissue turnover

2017 ◽  
Vol 232 (3) ◽  
pp. 493-500 ◽  
Author(s):  
Felipe de Oliveira Franco ◽  
Magno Alves Lopes ◽  
Felipe dos Santos Henriques ◽  
Rodrigo Xavier das Neves ◽  
Cesário Bianchi Filho ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Stromal Vascular Fraction ◽  
Body Weight Loss ◽  
Early Event ◽  
Mrna Levels ◽  
Adipose Tissue Depots ◽  
Cellular Turnover ◽  
Visceral Adipose ◽  
And Control

Cancer cachexia (CC) is a progressive metabolic syndrome that is marked by severe body weight loss. Metabolic disarrangement of fat tissues is a very early event in CC, followed by adipose tissue (AT) atrophy and remodelling. However, there is little information regarding the possible involvement of cellular turnover in this process. Thus, in this study, we evaluated the effect of CC on AT turnover and fibrosis of mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue depots as possible factors that contribute to AT atrophy. CC was induced by a subcutaneous injection of Walker tumour cells (2 × 107) in Wistar rats, and control animals received only saline. The experimental rats were randomly divided into four experimental groups: 0 days, 4 days, 7 days and 14 days after injection. AT turnover was analysed according to the Pref1/Adiponectin ratio of gene expression from the stromal vascular fraction and pro-apoptotic CASPASE3 and CASPASE9 from MEAT and RPAT. Fibrosis was verified according to the total collagen levels and expression of extracellular matrix genes. AT turnover was verified by measurements of lipolytic protein expression. We found that the Pref1/Adiponectin ratio was decreased in RPAT (81.85%, P < 0.05) with no changes in MEAT compared with the respective controls. CASPASE3 and CASPASE9 were activated on day 14 only in RPAT. Collagen was increased on day 7 in RPAT (127%) and MEAT (4.3-fold). The Collagen1A1, Collagen3A1, Mmp2 and Mmp9 mRNA levels were upregulated only in MEAT in CC. Lipid turnover was verified in RPAT and was not modified in CC. We concluded that the results suggest that CC affects RPAT cellular turnover, which may be determinant for RPAT atrophy.

Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1

2007 ◽  
Vol 293 (5) ◽  
pp. E1153-E1158 ◽  
Author(s):  
Hui Ren Zhou ◽  
Eun-Kyoung Kim ◽  
Hyojung Kim ◽  
Kate J. Claycombe
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Ex Vivo ◽  
Stromal Vascular Fraction ◽  
Tissue Cell ◽  
Mrna Levels ◽  
Cell Secretion ◽  
Monocyte Chemotactic Protein ◽  
Adipose Tissue Depots ◽  
Chemotactic Protein

Studies showed that monocyte chemotactic protein-1 (MCP-1) concentrations are increased in obesity. In our current study, we demonstrate that plasma MCP-1 level in leptin-deficient ob/ob mice is significantly higher than in lean mice. Furthermore, we determined that basal adipose tissue MCP-1 mRNA levels are significantly higher in ob/ob mice compared with lean mice. To determine the mechanisms underlying obesity-associated increases in plasma and adipose tissue MCP-1 levels, we determined adipose tissue cell type sources of MCP-1 production. Our data show that adipose tissue stem cells (CD34+), macrophages (F4/80+), and stromal vascular fraction (SVF) cells express significantly higher levels of MCP-1 compared with adipocytes under both basal and lipopolysaccharide (LPS)-stimulated conditions. Furthermore, basal and LPS-induced MCP-1 secretion levels were the same for both adipose F4/80+ and CD34+ cells, whereas adipose CD34+ cells have twofold higher cell numbers (30% of total SVF cells) compared with F4/80+ macrophages (15%). Our data also show that CD34+ cells from visceral adipose tissue depots secrete significantly higher levels of MCP-1 ex vivo when compared with CD34+ cells from subcutaneous adipose tissue depots. Taken together, our data suggest that adipose CD34+ stem cells may play an important role in obesity-associated increases in plasma MCP-1 levels.

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 Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity

2020 ◽  
Vol 21 (23) ◽  
pp. 9091
Author(s):  
Valentina Ceccarelli ◽  
Ilaria Barchetta ◽  
Flavia Agata Cimini ◽  
Laura Bertoccini ◽  
Caterina Chiappetta ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Insulin Signalling ◽  
Mrna Levels ◽  
Gamma Glutamyl Transpeptidase ◽  
Alcoholic Fatty Liver ◽  
Biliverdin Reductase ◽  
Omental Adipose Tissue ◽  
Obese Subjects ◽  
Visceral Adipose

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes’ size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02–1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76–1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

scholarly journals The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3195
Author(s):  
Yo-Han Han ◽  
Jeong-Geon Mun ◽  
Hee Dong Jeon ◽  
Dae Hwan Yoon ◽  
Byung-Min Choi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Uncoupling Protein ◽  
Body Weight Loss ◽  
In Vivo Experiments ◽  
Wasting Syndrome

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice

2008 ◽  
Vol 294 (5) ◽  
pp. E918-E927 ◽  
Author(s):  
David L. Allen ◽  
Allison S. Cleary ◽  
Kristin J. Speaker ◽  
Sarah F. Lindsay ◽  
Jill Uyenishi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Growth Inhibitor ◽  
Mrna Levels ◽  
Wild Type ◽  
Reporter Construct ◽  
High Fat ◽  
Visceral Adipose ◽  
Activin Receptor Iib

Myostatin (MSTN) is a secreted growth inhibitor expressed in muscle and adipose. We sought to determine whether expression of MSTN, its receptor activin RIIb (ActRIIb), or its binding protein follistatin-like-3 (FSTL3) are altered in subcutaneous or visceral adipose or in skeletal muscle in response to obesity. MSTN and ActRIIb mRNA levels were low in subcutaneous (SQF) and visceral fat (VF) from wild-type mice but were 50- to 100-fold higher in both SQF and VF from ob/ob compared with wild-type mice. FSTL3 mRNA levels were increased in SQF but decreased in VF in ob/ob compared with wild-type mice. Moreover, MSTN mRNA levels were twofold greater in tibialis anterior (TA) from ob/ob mice, whereas ActRIIb and FSTL3 mRNA levels were unchanged. MSTN mRNA levels were also increased in TA and SQF from mice on a high-fat diet. Injection of ob/ob mice with recombinant leptin caused FSTL3 mRNA levels to decrease in both VF and SQF in ob/ob mice; MSTN and ActRIIb mRNA levels tended to decrease only in VF. Finally, MSTN mRNA levels and promoter activity were low in adipogenic 3T3-L1 cells, but an MSTN promoter-reporter construct was activated in 3T3-L1 cells by cotransfection with the adipogenic transcription factors SREBP-1c, C/EBPα, and PPARγ. These results demonstrate that expression of MSTN and its associated binding proteins can be modulated in adipose tissue and skeletal muscle by chronic obesity and suggest that alterations in their expression may contribute to the changes in growth and metabolism of lean and fat tissues occurring during obesity.

scholarly journals Antioxidant Activity of Sprouts Extracts Is Correlated with Their Anti-Obesity and Anti-Inflammatory Effects in High-Fat Diet-Fed Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chung Shil Kwak ◽  
Mi-Ju Kim ◽  
Sunyeong Park ◽  
In Gyu Kim
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Mrna Levels ◽  
Adipocyte Size ◽  
Anti Inflammatory ◽  
Visceral Adipose

Obesity is closely associated with oxidative stress and chronic inflammation leading to related metabolic diseases. Some natural extracts or polyphenols reportedly possess anti-obesity and anti-inflammatory effects as well as antioxidant activity. In this study, we assessed the correlations between the antioxidant, anti-obesity, and anti-inflammatory activities of plant extracts with potent antioxidant activity in diet-induced obese mice. Sprouts of Cedrela sinensis (CS) and Oenothera biennis L. (OB) were selected as the most potent antioxidant plant based on analysis of in vitro antioxidant activity of the extracts of ten different edible plants. C57BL/6 mice were fed with a high-fat diet (HFD) and orally treated with 50% ethanol extract of CS or OB at 50 or 100 mg/kg body weight 5 days a week for 14 weeks. Body weight gain, weight of adipose tissue, adipocyte size, and levels of lipid metabolism, inflammation, and oxidative stress markers were investigated. The CS or OB extract reduced body weight gain, visceral adipose tissue weight, adipocyte size, and plasma leptin levels, and expressions of adipogenic genes (PPARγ and fatty acid synthase) in the adipose tissue and liver of HFD-fed mice. Both extracts also reduced mRNA levels of pro-inflammatory cytokines (IL-6 and TNF-α) and oxidative stress-related genes (heme oxygenase- (HO-) 1 and p40phox). Body weight gain of mice was significantly correlated with visceral adipose tissue weight and adipocyte size. Body weight gain and adipocyte size were significantly correlated with plasma total cholesterol and 8-epi PGF2α levels, mRNA levels of leptin, HO-1, p40phox, and CD-11 in the adipose tissue, and mRNA levels of TNF-α in the adipose tissue and liver. These results suggest that the CS and OB extracts with potent antioxidant activity may inhibit fat deposition in adipose tissue and subsequent inflammation.

scholarly journals A TRAIL-TL1A paracrine network involving adipocytes, macrophages and lymphocytes induces adipose tissue dysfunction downstream of E2F1 in human obesity

2020 ◽  
Author(s):  
Ada Admin ◽  
Nitzan Maixner ◽  
Tal Pecht ◽  
Yulia Haim ◽  
Vered Chalifa-Caspi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Metabolic Dysfunction ◽  
Trail Expression ◽  
Adipose Tissue Dysfunction ◽  
M1 Polarization ◽  
Tnf Superfamily ◽  
Diabetes Status ◽  
Elevated Expression ◽  
Visceral Adipose

Elevated expression of E2F1 in adipocyte-fraction of human visceral adipose-tissue(hVAT) associates with a poor cardio-metabolic profile. We hypothesized that beyond directly activating autophagy and MAP3K5(ASK)-MAP-kinase signaling, E2F1 governs a distinct transcriptome that contributes to adipose-tissue and metabolic dysfunction in obesity. We performed RNA-sequencing of hVAT samples from age-, sex- and BMI–matched patients, all obese, whose visceral-E2F1 protein expression was either high(E2F1<sup>high</sup>) or low(E2F1<sup>low</sup>). TNF-superfamily members, including <i>TRAIL</i>(<i>TNFSF10</i>), <i>TL1A</i>(<i>TNFSF15</i>) and their receptors were enriched in E2F1<sup>high</sup>. While <i>TRAIL</i> was equally expressed in adipocytes and stromal-vascular fraction(SVF), <i>TL1A </i>was mainly expressed in SVF, and TRAIL-induced <i>TL1A</i> was attributed to CD4+ and CD8<sup>+</sup>-subclasses of hVAT T-lymphocytes. In human adipocytes TL1A enhanced basal and impaired insulin-inhibitable lipolysis, and altered adipokine secretion, and in human macrophages induced foam-cells biogenesis and M1-polarization. Two independent human cohorts confirmed associations between TL1A and TRAIL expression in hVAT and higher leptin and IL6 serum concentrations, diabetes status, and hVAT-macrophage lipid content. Jointly, we propose an intra-adipose tissue E2F1-associated TNF-superfamily paracrine loop engaging lymphocytes, macrophages and adipocytes, ultimately contributing to adipose-tissue dysfunction in obesity.

Abstract 693: TLR3 Modulates Inflammation and Lipolysis in Visceral Adipose Tissue in High Fat Diet-fed Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Cuiqing Liu ◽  
Guohua Lin ◽  
Guoqing Zhang ◽  
Huanhuan Wang ◽  
Hongping Yin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
High Fat Diet ◽  
Dietary Factors ◽  
Whole Body ◽  
Mrna Levels ◽  
High Fat ◽  
M1 Macrophage ◽  
Visceral Adipose ◽  
Fat Feeding

Inflammation in insulin sensitive tissues, the visceral adipose tissue (VAT), is a central abnormality in obesity/insulin resistance (IR), with recruitment of innate immune cells such as monocytes into adipose tissue driving the development of glucose and lipoprotein dysregulation. We evaluated the role of Toll like receptor 3 (TLR3) in high fat diet-induced obesity and IR. Wild-type C57BL/6 and TLR3 -/- male mice were fed a high fat diet for 15 weeks. High fat feeding resulted in increased TLR3 expression in VAT. TLR3 deficiency attenuated the high fat diet-increased body weight, fasting blood glucose, whole body IR and impaired glucose tolerance. Morphologically, high fat diet induced adiposity and enlarged adipocyte area in VAT, which were attenuated in TLR3 -/- mice. Functionally, high fat diet induced dysregulation of adipocytokines such as downregulation of adiponectin and resistin, upregulation of leptin in VAT, with the disturbance of adiponectin and leptin was corrected in TLR3-/- mice. In addition, high fat diet inhibited insulin pathway, accompanied with decreased phosphorylation of AMPK and lowered expression of lipolysis-related enzymes such as HSL and ATGL, both at the mRNA levels and protein levels, all of which was corrected by TLR3 deficiency. Finally, TLR3 deletion suppressed the high fat feeding-mediated macrophage polarization, evidenced by increased type M1 macrophage (F4/80+/CD11c+/CD206-) infiltration and upregulation of M1 genes such as IL-6 and TNFα. TLR3 modulates high fat diet-induced IR and obesity by suppressing M1 macrophage-mediated VAT inflammation, facilitating secretion of adipocyte-derived hormones, thus enhanced AMPK activity and adipose lipolysis. These findings provide new mechanistic links between dietary factors-mediated IR and associated abnormalities in lipid metabolism and adipose inflammation.

scholarly journals Androgenic Influences on Behavior, Body Weight, and Body Composition in a Model of Chronic Social Stress

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 6145-6156 ◽  
Author(s):  
Mary M. N. Nguyen ◽  
Kellie L. K. Tamashiro ◽  
Susan J. Melhorn ◽  
Li Y. Ma ◽  
Stacy R. Gardner ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Composition ◽  
Body Weight ◽  
Adipose Tissue ◽  
Social Stress ◽  
Body Weight Loss ◽  
Oral Glucose ◽  
Lean Tissue ◽  
Chronic Social Stress ◽  
And Control

The visible burrow system (VBS) is a model used to study chronic social stress in colony-housed rats. A hierarchy develops among the males resulting in dominant (DOM) and subordinate (SUB) animals. Hierarchy-associated changes in body weight, body composition, behavior, and neuroendocrine measures have been observed. After 14 d of VBS housing, SUB animals have decreased body weight, elevated corticosterone, and decreased testosterone (T), compared with DOM animals and controls, placing SUB animals in an ideal endocrine state to regain lost body weight as adipose tissue. It is hypothesized that maintaining constant androgen concentrations in SUB males during stress will prevent body weight loss by maintaining more lean body mass. To test this, animals were gonadectomized and implanted with SILASTIC implants containing T, 5α-dihydrotestosterone (DHT), or cholesterol. Implants maintained constant physiological levels of T. Standard intact, T, and DHT implant colonies formed hierarchies, whereas cholesterol colonies did not. Androgen manipulations significantly altered offensive and defensive behaviors only on the first day of VBS housing. After VBS stress, intact, T, and DHT SUB animals weighed less and lost more adipose and lean tissue than DOM and control males, whereas DOM animals primarily lost adipose tissue. However, on recovery, DHT SUB animals maintained more lean tissue than intact SUB animals. Oral glucose tolerance tests revealed that glucose clears faster in stressed T-implanted males that have increased adipose tissue. Overall, these data suggest that constant androgen concentrations in SUB animals do not prevent weight loss and changes in body composition during stress but do so during recovery.

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