Palmitic Acid Targets Human Testicular Peritubular Cells and Causes a Pro-Inflammatory Response

Artur Mayerhofer,Henryk F Urbanski,Paul Kievit,Harald Welter,Matthias Trottmann,Frank-Michael Köhn,Ulrich Pickl,Kim-Gwendolyn Dietrich

doi:10.3390/jcm9082655

Abstract

Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 µM significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta (IL1beta) were not affected. The contractility marker calponin (CNN1) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys (n = 3), fed with a Western Style diet. They had elevated 2–5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated.

Highlights

There is evidence for a sterile type of inflammation in the testes of men suffering from idiopathic infertility [1,2,3]
This small testicular compartment in healthy, fertile men consists of elongated smooth muscle-like peritubular cells, i.e., contractile cells, which transport sperm and secrete extracellular matrix [3,4]
We reasoned that studies employing Human testicular peritubular cells (HTPCs) may be instructive and we examined actions of Palmitic acid (PA) in cultured HTPCs

Summary

Introduction

There is evidence for a sterile type of inflammation in the testes of men suffering from idiopathic infertility [1,2,3]. The changes are typical for a pro-inflammatory tissue environment and are predominantly observed in the peritubular wall This small testicular compartment in healthy, fertile men consists of elongated smooth muscle-like peritubular cells, i.e., contractile cells, which transport sperm and secrete extracellular matrix [3,4]. While the mentioned data mainly stem from animal studies, there is evidence for adverse effects of obesity on reproduction in men [29,30] They include lower testosterone levels and lower sperm counts, (see [31]). We reasoned that studies employing HTPCs may be instructive and we examined actions of PA in cultured HTPCs. In addition, expression levels of inflammatory genes in testes of three obese monkeys with elevated body fat and high circulating triglycerides were evaluated

Human Samples

Samples from Normal and Obese Monkeys

Statistical Analysis et

Obesity and Testicular IL6 Levels in Rhesus Monkeys