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.
University of Texas Southwestern Medical Center, Dallas, TX 75390-8854, USA. roger.unger@UTSouthwestern.edu
Roger H
RH
Unger
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