scholarly journals Substance P (SP)-Neurokinin-1 Receptor (NK-1R) Alters Adipose Tissue Responses to High-Fat Diet and Insulin Action

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2197-2205 ◽  
Author(s):  
Iordanes Karagiannides ◽  
Dimitris Stavrakis ◽  
Kyriaki Bakirtzi ◽  
Efi Kokkotou ◽  
Tamara Pirtskhalava ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Protein Kinase ◽  
Substance P ◽  
High Fat Diet ◽  
High Fat ◽  
Tissue Responses ◽  
Mesenteric Fat ◽  
Neurokinin 1 ◽  
Circulating Levels

Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD). Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses. NK-1R KO and wild-type (WT) littermates were fed a HFD for 3 wk, and obesity-associated responses were determined. Compared with WT, NK-1 KO mice show reduced weight gain and circulating levels of leptin and insulin in response to HFD. Adiponectin receptor mRNA levels are higher in mesenteric fat and liver in NK-1 KO animals compared with WT, after HFD. Mesenteric fat from NK-1R KO mice fed with HFD has reduced stress-activated protein kinase/c-Jun N-terminal kinase and protein kinase Cθ activation compared with WT mice. After glucose challenge, NK-1R KO mice remove glucose from the circulation more efficiently than WT and pair-fed controls, suggesting an additional peripheral effect of NK-1R-mediated signaling on glucose metabolism. Glucose uptake experiments in isolated rat adipocytes showed that SP directly inhibits insulin-mediated glucose uptake. Our results further establish a role for SP-NK-1R interactions in adipose tissue responses, specifically as they relate to obesity-associated pathologies such as glucose intolerance and insulin resistance. Our results highlight this pathway as an important therapeutic approach for type 2 diabetes.

scholarly journals Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5390
Author(s):  
Qianhui Zeng ◽  
Nannan Wang ◽  
Yaru Zhang ◽  
Yuxuan Yang ◽  
Shuangshuang Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Glycolipid Metabolism ◽  
Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rieko Takanabe ◽  
Koh Ono ◽  
Tomohide Takaya ◽  
Takahiro Horie ◽  
Hiromichi Wada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Control Cell ◽  
High Fat ◽  
Expression Levels ◽  
Mesenteric Fat ◽  
Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

scholarly journals Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianfei Lai ◽  
Qianyu Qian ◽  
Qinchao Ding ◽  
Li Zhou ◽  
Ai Fu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Sirtuin 1 ◽  
Male Mice ◽  
High Fat ◽  
Sirt1 Expression ◽  
Salvianolic Acid ◽  
Amp Activated Protein Kinase

Background: Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure.Purpose: The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning.Methods: Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated.Resluts: Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1.Conclusion: Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.

scholarly journals A High-Fat Diet Attenuates Amp-Activated Protein Kinase α1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development in Vivo

2020 ◽  
Author(s):  
Ada Admin ◽  
Chenghui Yan ◽  
Xiaoxiang Tian ◽  
Jiayin Li ◽  
Dan Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Liver Development ◽  
High Fat ◽  
Tissue Specific ◽  
Nonalcoholic Fatty Liver ◽  
Amp Activated Protein Kinase

Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (<a>AT</a>) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (<a>NAFLD</a>). Exosome components, liver fat content, and liver function were monitored in AT in mice fed a <a>high-fat diet </a>(<a>HFD</a>) or treated with metformin- or GW4869 and with AMP-activated protein kinase (AMPKα1)<i> </i>floxed<i> (Prkaα1</i><sup>fl/fl</sup>/WT), <a><i>Prkaα1</i><sup>-/-</sup></a>, liver tissue-specific <i>Prkaα1</i><sup>-/-</sup>, or AT-specific <i>Prkaα1</i><sup>-/-</sup> modification. In cultured adipocytes and white adipose tissue (WAT), the absence of <a><i>AMPKα1</i></a> increased exosome release and exosomal proteins by elevating <a>tumor susceptibility gene 101 (<i>TSG101</i></a>)-mediated exosome biogenesis. In adipocytes treated with palmitic acid, TSG101 facilitated scavenger receptor class B (CD36) sorting into exosomes. CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation. Consistently, an HFD induced more severe lipid accumulation and cell death in <a><i>Prkaα1</i><sup>-/-</sup> </a>and adipose tissue-specific <i>Prkaα1</i><sup>-/-</sup> mice than in WT and liver-specific <i>Prkaα1</i><sup>-/-</sup> mice. AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver specific <i>Prkaα1</i><sup>-/-</sup> mice. Moreover, administration of the exosome inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers in <i>Prkaα1</i><sup>-/-</sup> and adipocyte-specific <i>Prkaα1</i><sup>-/-</sup> mice. We conclude that HFD-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT C<a>D36</a>-containing exosomes.

scholarly journals Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity

2021 ◽  
Author(s):  
Camila Queiroz-Glauss ◽  
Mariana Vieira ◽  
Marcela Helena Gonçalves-Pereira ◽  
Stephanie Almeida ◽  
Rachel Freire ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Experimental Studies ◽  
Treg Cells ◽  
Loss Of Function ◽  
High Fat ◽  
Diet Induced Obesity ◽  
And Function

Background: Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms induced by the parasite that regulate the development of metabolic diseases in the host are unclear. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. Principal Findings: The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by higher levels of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also revert the loss of function in Tregs associated with high fat diet. Conclusion: These data suggest that H. polygyrus infection can prevent weight gain and metabolic syndrome in animals fed with high fat diet associated with modulations of adipose tissue Treg cells.

scholarly journals Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

Nutrients ◽  
2016 ◽  
Vol 8 (10) ◽  
pp. 594 ◽  
Author(s):  
Karen Kelly ◽  
John Kennelly ◽  
Marta Ordonez ◽  
Randal Nelson ◽  
Kelly Leonard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Folic Acid ◽  
Weight Gain ◽  
High Fat Diet ◽  
Lipid Storage ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation

scholarly journals Deletion of the gene encoding G0/G1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice

Diabetologia ◽  
2014 ◽  
Vol 58 (1) ◽  
pp. 149-157 ◽  
Author(s):  
Wissal El-Assaad ◽  
Karim El-Kouhen ◽  
Amro H. Mohammad ◽  
Jieyi Yang ◽  
Masahiro Morita ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Weight Gain ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Gene Encoding

scholarly journals Time-Restricted Feeding Restores Obesity-Induced Alteration in Adipose Tissue Immune Cell Phenotype

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3780
Author(s):  
Youngyoon Lee ◽  
Yelim Kim ◽  
Minam Lee ◽  
Dayong Wu ◽  
Munkyong Pae
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
High Fat Diet ◽  
Immune Cell ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Restricted Feeding ◽  
High Fat ◽  
Low Fat Diet ◽  
Adipose Tissue Macrophages

Studies suggest that time-restricted feeding (TRF) may prevent obesity and its commodities. At present, little is known about how TRF impacts immune cells, and whether such an effect is linked to altered metabolic parameters under condition of a high-fat diet (HFD)-induced obesity. To address these issues, we conducted a study in which we determined whether TRF has therapeutic efficacy against weight gain, adiposity, as well as associated immune cell disturbance found in obese mice. Six-week-old male C57BL/6 mice were fed a low-fat diet (LFD) or HFD ad libitum for six weeks, after which time a subgroup of HFD mice was switched to the 10 h TRF paradigm (HFD-TRF) for additional eight weeks. We found that TRF intervention reduced HFD-induced weight gain. Even with comparable fat mass and mean adipocyte area, the HFD-TRF group had lower mRNA levels of proinflammatory cytokine Tnfα and chemokine Ccl8, along with reduced numbers of adipose tissue macrophages (ATM), CD11c+ ATM, and CD8+ T cell compared to the HFD group, while maintaining CD8+ to CD4+ ratio at levels similar to those in the LFD group. Furthermore, TRF intervention was effective in improving glucose tolerance and reducing HOMA-IR. Taken together, our findings suggest that TRF restores the obesity-induced alteration in immune cell composition, and this effect may in part contribute to health benefits (including insulin sensitivity) of practicing TRF.

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