Lipid overload and overflow: metabolic trauma and the metabolic syndrome.
Approximately two-thirds of the US population are overweight, which means that insulin resistance is probably the most common metabolic abnormality in the USA. I propose three novel concepts concerning the causes and consequences of insulin resistance that challenge current thinking. First, there is the evidence that resistance to insulin-stimulated glucose metabolism is not a primary event in obesity, but is secondary to lipid accumulation resulting from full responsiveness to insulin-stimulated lipogenic activity. Second, resistance to insulin-stimulated glucose metabolism, now considered detrimental to health, might be a protective mechanism that reduces lipid-induced damage to tissue by excluding glucose from cells, thus decreasing glucose-derived lipogenesis. Third, I suggest that lipid-induced insulin resistance and the accompanying metabolic syndrome are secondary to leptin resistance, resulting in breakdown in the normal partitioning of surplus lipids in the adipocyte compartment.
Unger
Roger H
RH
University of Texas Southwestern Medical Center, Dallas, TX 75390-8854, USA. roger.unger@UTSouthwestern.edu
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D051381:Rats
D001786:Blood Glucose; D020738:Leptin