Lipid metabolism and nutrient partitioning strategies.
The increasing prevalence of overweight and obesity worldwide is daunting and requires prompt attention by the affected, health care profession, government and the pharmaceutical industry. Because overweight/obesity are defined as an excess of adipose tissue mass, all approaches in prevention and treatment must consider redirecting lipid storage in adipose tissue to oxidative metabolism. Lipid partitioning is a complex process that involves interaction between fat and other macronutrients, particularly carbohydrate. In an isocaloric environment, when fat is stored carbohydrate is oxidized and vice versa. Processes that influence fat partitioning in a manner in which weight is maintained must be modified by changes in organ-specific fat transport and metabolism. When therapy is considered, however, changes in lipid partitioning alone will be ineffective unless a negative energy balance is also achieved, i.e. energy expenditure exceeds energy intake. The intent of this review is to focus on molecules including hormones, enzymes, cytokines, membrane transport proteins, and transcription factors directly involved in fat trafficking and partitioning that could be potential drug targets. Some examples of favorably altering body composition by systemic and/or tissue specific modification of these molecules have already been provided with gene knockout and/or transgenic approaches in mice. The translation of this science to humans remains a challenging task.
Morris
A M
AM
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Calsbeek
D J
DJ
Eckel
R H
RH
D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D004032:Diet; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008053:Lipid Mobilization / Q000502:physiology; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism
D019440:Anti-Obesity Agents; D047492:Peroxisome Proliferator-Activated Receptors; D006003:Glycogen; D005947:Glucose