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DGAT and triglyceride synthesis: a new target for obesity treatment?

H C Chen1, R V Farese

  • 1Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100, USA. hcc1@itsa.ucsf.edu

Insights

Inhibiting triglyceride synthesis, previously unexplored for obesity, is now feasible. Blocking the enzyme DGAT in mice prevented obesity by increasing energy expenditure, suggesting a novel therapeutic approach.

Area of Science:

  • Biochemistry
  • Metabolic disease research
  • Obesity therapeutics

Background:

  • Triglycerides are vital for survival.
  • Triglyceride synthesis was thought to be a single, unmodifiable pathway.
  • Inhibiting triglyceride synthesis for obesity treatment was largely unexplored.

Purpose of the Study:

  • To investigate the feasibility of targeting triglyceride synthesis for obesity treatment.
  • To explore the role of acyl CoA:diacylglycerol acyltransferase (DGAT) in obesity.

Main Methods:

  • Studied mice genetically engineered to lack DGAT, a key enzyme in triglyceride synthesis.
  • Assessed the viability and obesity resistance of DGAT-deficient mice.
  • Investigated the underlying mechanisms of obesity resistance.

Main Results:

  • Mice lacking DGAT were viable.
  • DGAT-deficient mice exhibited resistance to diet-induced obesity.
  • Obesity resistance was unexpectedly linked to increased energy expenditure.

Conclusions:

  • Targeting specific components of triglyceride synthesis, like DGAT, is a viable strategy.
  • Inhibiting DGAT offers a novel potential therapeutic approach for obesity.
  • Increased energy expenditure is a key factor in DGAT-mediated obesity resistance.

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