Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-α: Independent and interactive roles in the regulation of lipid metabolism

Harini Sampath, James M. Ntambi

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: With the increasing incidence of obesity today, related complications such as diabetes, insulin resistance and hepatic steatosis are also becoming major concerns. Since these conditions share a common factor, aberrations in lipid metabolism, understanding the molecular changes that lead to abnormal lipid partitioning has become key to combating the obesity epidemic. RECENT FINDINGS: The enzyme stearoyl-coenzyme A desaturase 1 (SCD1) has been shown to be intimately involved in both the lipogenic as well as the lipid oxidative pathways. Our studies with the SCD1 mouse model have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity. Consequently, they also show greater whole body insulin sensitivity than wild-type mice. SCD1 mice have decreased expression of genes of lipogenesis and increased expression of lipid oxidative genes. The main transcription factors controlling genes of lipid synthesis and oxidation are sterol regulatory element binding protein-1c and peroxisome proliferator- activated receptor-α (PPARα), respectively. Here, we review some studies that show that the effects of SCD1 deficiency on whole body adiposity may be partly dependent on sterol regulatory element binding protein-1c, but are most likely independent of peroxisome proliferator-activated receptor-α. SUMMARY: Our findings indicate that SCD1 is a key controller of lipid partitioning between lipogenesis and oxidation. While some questions regarding the molecular changes downstream of SCD1 deletion are yet to be answered, the studies outlined below clearly point to SCD1 as a highly promising target in combating obesity as well as related complications.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
JournalCurrent Opinion in Clinical Nutrition and Metabolic Care
Volume9
Issue number2
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Sterol Regulatory Element Binding Protein 1
stearoyl-CoA desaturase
Peroxisome Proliferator-Activated Receptors
Lipid Metabolism
lipid metabolism
sterols
binding proteins
Lipids
obesity
Obesity
lipids
Lipogenesis
lipogenesis
insulin resistance
Insulin Resistance
Enzymes and Coenzymes
oxidation
fatty liver
mice
Adiposity

Keywords

  • Insulin resistance
  • Lipid oxidation
  • Lipogenesis
  • Obesity
  • Transcription factors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Stearoyl-coenzyme A desaturase 1, sterol regulatory element binding protein-1c and peroxisome proliferator-activated receptor-α: Independent and interactive roles in the regulation of lipid metabolism",
abstract = "PURPOSE OF REVIEW: With the increasing incidence of obesity today, related complications such as diabetes, insulin resistance and hepatic steatosis are also becoming major concerns. Since these conditions share a common factor, aberrations in lipid metabolism, understanding the molecular changes that lead to abnormal lipid partitioning has become key to combating the obesity epidemic. RECENT FINDINGS: The enzyme stearoyl-coenzyme A desaturase 1 (SCD1) has been shown to be intimately involved in both the lipogenic as well as the lipid oxidative pathways. Our studies with the SCD1 mouse model have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity. Consequently, they also show greater whole body insulin sensitivity than wild-type mice. SCD1 mice have decreased expression of genes of lipogenesis and increased expression of lipid oxidative genes. The main transcription factors controlling genes of lipid synthesis and oxidation are sterol regulatory element binding protein-1c and peroxisome proliferator- activated receptor-α (PPARα), respectively. Here, we review some studies that show that the effects of SCD1 deficiency on whole body adiposity may be partly dependent on sterol regulatory element binding protein-1c, but are most likely independent of peroxisome proliferator-activated receptor-α. SUMMARY: Our findings indicate that SCD1 is a key controller of lipid partitioning between lipogenesis and oxidation. While some questions regarding the molecular changes downstream of SCD1 deletion are yet to be answered, the studies outlined below clearly point to SCD1 as a highly promising target in combating obesity as well as related complications.",
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