Loss of Stearoyl-CoA Desaturase-1 Attenuates Adipocyte Inflammation

Liu, Xueqing; Miyazaki, Masaru; Flowers, Matthew T.; Sampath, Harini; Zhao, Minghui; Chu, Kengyeh K.; Paton, Chad M.; Joo, Diane Seohee; Ntambi, James M.

doi:10.1161/atvbaha.109.195636

Cited by 71 publications

(66 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SCD1 is highly expressed in both white and brown adipose tissue. Previous studies in mice with a whole-body deletion of SCD1 have documented increased insulin signaling and uncoupling protein expression in the white and brown adipose tissue (15)(16)(17). Due to the simultaneous deletion of Scd1 from all tissues in GKO mice, it is unclear whether metabolic changes in a particular tissue are a direct effect of local loss of SCD1 function or an indirect effect stemming from loss of SCD1 in distal tissues.…”

Section: Discussionmentioning

confidence: 99%

Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity

Flowers

Ade

Strable

et al. 2012

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org occurring Scd1 mutations and those with global deletion of Scd1 (GKO mice) ( 1-3 ). These mice display a remarkable hypermetabolic phenotype that protects them from obesity, insulin resistance, and hepatic steatosis. To determine which tissue or tissues are primarily responsible for these metabolic changes, we have employed the Crelox system to explore the tissue-specifi c contributions of SCD1.We previously found that mice with a liver-specifi c deletion of Scd1 (LKO mice) are protected from high-carbohydrate, but not high-fat, diet-induced obesity (DIO), unlike GKO mice that are resistant to both high-fat and highcarbohydrate DIO ( 4 ). This indicates that inhibition of liver SCD1 alone is insuffi cient to elicit the hypermetabolism and increased energy expenditure necessary to compensate for the increased energy intake associated with high-fat feeding. The reduced high-carbohydrate dietinduced adiposity in LKO and GKO mice was associated with a block in carbohydrate-induced increases in hepatic sterol regulatory element binding protein-1c (SREBP-1c) proteolytic processing, expression of FA synthesis genes, and hepatic triglyceride (TG) accumulation. We recently reported that mice with a skin-specifi c deletion of Scd1 (SKO mice) recapitulated the hypermetabolic phenotype observed in GKO mice, indicating that the skin is a major contributor to the altered energy metabolism observed in GKO mice ( 5 ). In contrast, SKO mice had normal carbohydrate-induced increase in SREBP-1c maturation and FA synthesis genes. These hepatic observations highlight that not all of the phenotypes of the SCD1 GKO mice can be attributed to SCD1 deletion in the skin.Interestingly, mice intraperitoneally injected with Scd1 -targeted antisense oligonucleotides (ASO) are also protected from the development of high-fat DIO and insulin -DK-062388 (to J.M.N.), ; and by an American Heart Association postdoctoral fellowship (to M.T.F.) Abbreviations: a/a, non-agouti; A y /a, agouti; AKO, adipose SCD1 knockout; ASO, antisense oligonucleotide; DIO, diet-induced obesity; GKO, global SCD1 knockout; LAKO, liver/adipose SCD1 knockout; LKO, liver SCD1 knockout; Lox, Scd1 fl ox/fl ox ; SCD1, stearoyl-CoA desaturase-1; SKO, skin SCD1 knockout; SREBP1c, sterol regulatory element binding protein-1c; TG, triglyceride.

show abstract

Section: Discussionmentioning

confidence: 99%

Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity

Flowers

Ade

Strable

et al. 2012

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…address the direct effects of adipocyte factors generated in response to PFKFB3/iPFK2 overexpression on hepatocyte metabolic and inflammatory responses, adipocyte-conditioned medium was used to treat WT mouse primary hepatocytes as described previously (11,33,34). Palmitate was supplemented into hepatocyte medium to induce fat deposition and inflammatory responses.…”

Section: Adipocyte-derived Factors Dissociate Hepatocyte Inflammatorymentioning

confidence: 99%

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses

Huo

Guo

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Inducible 6-phosphofructo-2-kinase links metabolic and inflammatory responses. Results: Adipose overexpression of inducible 6-phosphofructo-2-kinase increases fat deposition, suppresses inflammatory responses, and improves insulin sensitivity in both adipose and liver tissues. Conclusion: Inducible 6-phosphofructo-2-kinase in adipocytes uniquely dissociates diet-induced inflammatory and metabolic responses in both adipose and liver tissues. Significance: Adipocyte-inducible 6-phosphofructo-2-kinase may underlie healthy obesity.

show abstract

“…This work has demonstrated that reductions in Scd1 expression in both the AT and the liver could improve insulin sensitivity [19,156,158]. In a separate study, Scd1-/-mice fed a high-fat diet had improved basal insulin signalling in epididymal AT compared to wild type mice [120,159]. This same study also showed that epididymal AT from Scd1-/-mice fed the same high-fat diet had reduced inflammation when compared to wild type AT.…”

Section: Ii) Scd1 In Rodent Adipose Tissuementioning

confidence: 69%

“…This same study also showed that epididymal AT from Scd1-/-mice fed the same high-fat diet had reduced inflammation when compared to wild type AT. Specifically, they saw a reduction in AT cell death, as well as decreased expression of Mcp-1, Tnfα and vascular cell adhesion molecule 1 (Vcam-1) [120].…”

Section: Ii) Scd1 In Rodent Adipose Tissuementioning

confidence: 99%

Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

Ralston

2015

Appl. Physiol. Nutr. Metab.

View full text Add to dashboard Cite

Worldwide obesity rates have risen to epidemic proportions, with over 600 million obese individuals across the globe. These individuals are prone to obesity-related health complications including type 2 diabetes, hypertension, cancer and cardiovascular disease. Obesity also coincides with the expansion of adipose tissue (AT), which has an important role storing excess calories in the form of triacylglycerol (TAG) within adipocyte lipid droplets. The predominant fatty acids (FAs) comprising adipocyte TAGs are monounsaturated FAs (MUFAs), which are produced by stearoyl-CoA desaturase 1 (SCD1). Specifically, SCD1 converts saturated FAs palmitate (PA) and stearate (SA) into palmitoleate (PMA) and oleate (OA), respectively.Interestingly, whole-body SCD1-deficiency is associated with reduced lipogenesis and adiposity.This places SCD1 as a potential target for obesity therapies; however, our understanding of the mechanisms linking SCD1 with changes in adipocyte function remains unclear. This thesis provides important new insights into how SCD1 impacts adipocyte FA metabolism and cellular function. Using a specific SCD1 inhibitor, changes in lipid metabolism, global gene expression, inflammation, cellular stress and basal insulin signaling were assessed in 3T3-L1 adipocytes.Results demonstrated that SCD1 inhibition caused a reduction in TAGs and phospholipids, which coincided with the down-regulation of genes associated with the biosynthesis of these lipid fractions. Cellular diacylglyerols were increased with SCD1 inhibition and insulin signaling was partially impaired. In contrast, markers of cellular stress were unaltered. Furthermore, the FA composition of each lipid fraction was dramatically modified, with SCD1-inhibited adipocytes specifically up-regulating the elongation of PA to SA. Stable isotope tracer experiments revealed that this elongation was occurring via elongase 6. Additionally, reduced SCD1 activity in adipocytes exacerbated the effects of exogenous SA on markers or inflammation. Taken together, SCD1 activity has many indirect influences on adipocyte metabolism in addition to its role in FA desaturation. Importantly, SCD1 facilitates the storage of FAs in TAGs and the ability of adipocytes to handle exogenous FAs. SCD1 also prevents saturated FA and DAG accumulation, and preserves insulin signaling in adipocytes. Ultimately this thesis highlights the importance of SCD1 in the maintenance of adipocyte cellular function, and emphasizes the wide-ranging impact of SCD1 on adipocyte FA metabolism.iv

show abstract

Loss of Stearoyl-CoA Desaturase-1 Attenuates Adipocyte Inflammation

Cited by 71 publications

References 35 publications

Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity

Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses

Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

Contact Info

Product

Resources

About