Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse

Diabetologia. 2005 Jun;48(6):1059-65. doi: 10.1007/s00125-005-1765-8. Epub 2005 May 3.

Abstract

Aims/hypothesis: Dietary supplementation with conjugated linoleic acids (CLA) has a fat-reducing effect in various species, but induces severe hyperinsulinaemia and hepatic steatosis in the mouse. This study aimed to determine the causes of the deleterious effects of CLA on insulin homeostasis.

Methods: The chronology of adipose and liver weight, hepatic triglyceride accumulation and selected blood parameters, including lipids, insulin, leptin and adiponectin, was determined in C57BL/6J female mice fed a 1% isomeric mixture of CLA for various periods of time ranging from 2 to 28 days. Insulin secretion was measured in 1-h static incubations of pancreatic islets, and pancreas morphometric parameters were determined in mice fed CLA for 28 days.

Results: Plasma levels of leptin and adiponectin sharply decreased after 2 days of CLA feeding, although adipose tissue mass only decreased after day 6. Hyperinsulinaemia developed at day 6 and consistently worsened up to day 28, in parallel with increases in hepatic lipid content. Islets from CLA-fed mice displayed three- to four-fold increased rates of glucose-stimulated insulin secretion, both in the absence and presence of isobutyl methylxanthine or carbachol. The increased insulin-releasing capacity of islets from CLA-fed mice was explained by an increase in beta cell mass and number.

Conclusions/interpretation: The data suggest that CLA supplementation induces a profound reduction of leptinaemia and adiponectinaemia, followed by hyperinsulinaemia due to the increased secretory capacity of pancreatic islets, leading, in turn, to liver steatosis. These observations cast doubt on the safety of dietary supplements containing CLA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin
  • Adipose Tissue / anatomy & histology
  • Animals
  • Body Weight
  • Disease Models, Animal
  • Female
  • Hyperinsulinism / chemically induced*
  • Hyperplasia
  • Insulin / metabolism
  • Insulin Secretion
  • Intercellular Signaling Peptides and Proteins / blood*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology*
  • Leptin / blood*
  • Linoleic Acids, Conjugated / adverse effects*
  • Liver / anatomy & histology
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Organ Size
  • Triglycerides / metabolism

Substances

  • Adiponectin
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Leptin
  • Linoleic Acids, Conjugated
  • Triglycerides