Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and relationship with adipose TNFα expression

Subramanian Ranganathan,Margherita Maffei,Philip A Kern

doi:10.1016/s0022-2275(20)32561-x

Subramanian Ranganathan, Margherita Maffei + Show 1 more

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https://doi.org/10.1016/s0022-2275(20)32561-x

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Abstract

Elevated plasma leptin levels are found in obese humans, suggesting a defect in the function of leptin in regulating body weight and adiposity. In 53 subjects covering a broad range of adiposity, we examined the relationships between plasma leptin, adipose tissue ob mRNA levels, and adipose tissue TNF mRNA. There was a highly significant correlation between plasma leptin levels and every index of adiposity. In contrast, the relationship between ob mRNA levels and adiposity was weak. Adipose tissue from obese subjects demonstrated higher ob mRNA levels than adipose tissue from lean subjects (lean: 0.49 ± 0.05; obese 0.87 ± 0.09 arbitrary units, P < 0.05). However, there was no significant correlation between body fat and ob mRNA level. In addition, there was no significant relationship between ob mRNA levels and plasma leptin levels, which were measured in the same subjects. In addition to the measure of ob mRNA levels, adipose TNF mRNA levels were measured in 18 subjects. TNF mRNA levels varied with ob mRNA levels (r = 0.44, P = 0.06). These data show that plasma leptin levels are not directly related to adipose tissue ob mRNA levels, suggesting posttranscriptional regulation of leptin expression, either at the level of the adipocyte, or by alteration of plasma leptin degradation or clearance. In addition, the parallel changes in ob and TNF mRNA in adipose tissue suggest that these two important factors in the defense against obesity may be regulated similarly.—Ranganathan, S., M. Maffei, and P. A. Kern. Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and relationship with adipose TNFα expression. J. Lipid Res. 1998. 39: 724–730.

Highlights

Elevated plasma leptin levels are found in obese humans, suggesting a defect in the function of leptin in regulating body weight and adiposity
There was a significant relationship between plasma leptin and body mass index (BMI) (r ϭ 0.711, P Ͻ 0.0001), and between plasma leptin and total body fat (r ϭ 0.761, P Ͻ 0.0001)
When patients were divided into lean and obese, ob mRNA levels were significantly higher in obese subjects (Fig. 1)

Summary

Introduction

Elevated plasma leptin levels are found in obese humans, suggesting a defect in the function of leptin in regulating body weight and adiposity. Several studies have demonstrated that adipose tissue ob mRNA and plasma leptin levels are elevated in obese rodents [10,11,12,13,14,15]. Because of the consistent finding of elevated plasma leptin, there is a tendency to assume that plasma leptin levels are directly related to adipose tissue ob gene expression Another important product of the adipocyte is TNF␣, which is elevated in the adipose tissue of obese rodents and humans [22,23,24], and which may play an important role in obesity-related insulin resistance [25]. We found a remarkable lack of correlation between adipose tissue expression and plasma leptin, suggesting that other factors are involved in the regulation of plasma leptin levels

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