Lipid Overload and Overflow: Metabolic Trauma and the Metabolic Syndrome

Trends Endocrinol Metab. 2003 Nov;14(9):398-403. doi: 10.1016/j.tem.2003.09.008.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Humans
  • Insulin Resistance / physiology*
  • Leptin / physiology*
  • Lipid Metabolism*
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / physiopathology*
  • Obesity / complications
  • Obesity / physiopathology*
  • Rats

Substances

  • Blood Glucose
  • Leptin