Human Serum Adiponectin Levels are not Under Short-Term Negative Control by Free Fatty Acids in Vivo

Introduction

Plasma levels of free fatty acids (FFAs) are elevated when adipose tissue expands and adipocytes become refractory to inhibition of lipolysis by insulin. FFAs have been known for years to have multiple effects on peripheral tissues such as glucose uptake and glycogen synthesis inhibition in skeletal muscle, hepatic gluconeogenesis stimulation, and insulin clearance impairment, altogether favoring whole body insulin resistance, hyperinsulinemia, hyperglycemia, and finally type 2 diabetes mellitus. Besides these metabolic effects, FFAs seem to be able to regulate adipocytokine gene expression. FFAs were shown to repress the expression of the recently discovered adipocyte hormone resistin in an insulin-resistant rat model [1]. In in vitro differentiated adipocytes, FFAs also downregulated the expression of leptin, the most important central regulator of energy expenditure and food intake known to date [2]. This effect of FFAs on gene expression might be mediated by direct activation of specific fatty acid-regulated transcription factors (for review, see [3]).

Another very interesting secreted adipocyte product is adiponectin. Plasma concentrations of this protein were found to correlate inversely with obesity, insulin resistance, hyperinsulinemia, and coronary heart disease [4] [5]. Moreover, adiponectin has been reported to decrease plasma glucose levels in diabetic mice by enhancement of the suppressive action of insulin on hepatic gluconeogenesis [6]. Stimulation of skeletal muscle fatty acid oxidation might also contribute to this adiponectin-mediated increase in insulin sensitivity [7]. Among the hormones known to play a role in insulin resistance, insulin, tumor necrosis factor-α, and glucocorticoids have been reported to modulate adipocyte expression of adiponectin [8] [9]. The impact of FFAs on adiponectin expression and adiponectin levels in serum has not as yet been studied in humans.

To investigate whether FFAs reduce serum adiponectin levels in humans, we screened subjects with artificially provoked high and low serum levels of FFAs.

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