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Updated: Aug 20, 2026
Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation
1Department of Clinical Biochemistry and Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Abstract:
Obesity and type 2 diabetes mellitus are the major noncommunicable public health problem of the 21st century. The best strategy to tackle this problem is to develop strategies to prevent/treat obesity. However, it is becoming clear that despite successful research identifying weight regulatory pathways, the development of the obesity epidemic is outpacing scientific progress. The lack of success controlling the obesity epidemic in an aging population will result in another subsequent uncontrolled epidemic of complications. Our research focuses on the mechanisms causing lipotoxicity aiming to identify suitable strategies to prevent or at least retard the development of the metabolic syndrome. Previous work using transgenic and knockout mouse models has shown an interplay between white adipose tissue and skeletal muscle linking fatty acid (FA) synthesis with reciprocal effects on FA oxidation. Work from our lab and others suggests that defective adipose tissue is a key link between obesity, insulin resistance and type 2 diabetes mellitus by promoting the development of lipotoxicity in peripheral tissues. We propose a series of models to describe the process by which the adipose tissue could react to an energy-rich environment and responds depending on genetic and physiological factors, impacting on the functions of other peripheral tissues. We suggest that by examining hypotheses that encompass multiple organs and the partitioning of energy between these organs, a suitable strategy can be devised for the treatment of chronic obesity.
Insights
Obesity and type 2 diabetes are major health issues. Research suggests defective adipose tissue promotes lipotoxicity, contributing to insulin resistance and metabolic syndrome, offering new treatment targets.
Area of Science:
- Metabolic disorders
- Public health
- Obesity research
Background:
- Obesity and type 2 diabetes mellitus (T2DM) represent significant global public health challenges.
- Despite advances in understanding weight regulation, the obesity epidemic continues to grow, particularly in aging populations.
- This escalating epidemic forecasts a rise in associated complications, including metabolic syndrome.
Purpose of the Study:
- To investigate the mechanisms underlying lipotoxicity.
- To identify strategies for preventing or delaying the onset of metabolic syndrome.
- To understand the role of adipose tissue dysfunction in obesity, insulin resistance, and T2DM.
Main Methods:
- Utilizing transgenic and knockout mouse models to study the interplay between white adipose tissue and skeletal muscle.
- Analyzing fatty acid (FA) synthesis and oxidation pathways.
- Developing models to describe adipose tissue response to energy-rich environments and its impact on peripheral tissues.
Main Results:
- Evidence indicates an interaction between white adipose tissue and skeletal muscle concerning FA metabolism.
- Defective adipose tissue is implicated as a critical factor linking obesity, insulin resistance, and T2DM.
- Lipotoxicity in peripheral tissues is promoted by adipose tissue dysfunction.
Conclusions:
- Adipose tissue plays a central role in metabolic syndrome development through lipotoxicity.
- Understanding how adipose tissue responds to energy excess, influenced by genetic and physiological factors, is crucial.
- Multi-organ hypotheses examining energy partitioning may yield effective strategies for managing chronic obesity.
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