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Decreased lipin 1β expression in visceral adipose tissue is associated with insulin resistance in polycystic ovary syndrome

Barbara Mlinar, Marija Pfeifer¹, Eda Vrtanik-Bokal², Mojca Jensterle¹ and Janja Marc

Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Akereva 7, SI-1000 Ljubljana, Slovenia¹ Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloka 7, SI-1000 Ljubljana, Slovenia² Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, lajmerjeva 3, SI-1000 Ljubljana, Slovenia

(Correspondence should be addressed to J Marc; Email: janja.marc{at}ffa.uni-lj.si)

Objective: In polycystic ovary syndrome (PCOS), insulin resistance (IR) appears with high prevalence and represents the major cause of cardiometabolic complications. Lipin 1β regulates lipid metabolism and augments insulin sensitivity. The impact of lipin 1β expression in visceral and subcutaneous adipose tissue of PCOS patients on IR was studied for the first time.

Methods: Eighty-five PCOS patients and 44 controls were enrolled for subcutaneous tissue biopsy, of whom 25 patients and 30 controls also underwent visceral adipose tissue biopsy. Gene expression of lipin 1β was measured, together with that of peroxisome proliferator-activated receptor , lipoprotein lipase, hormone-sensitive lipase, adiponectin and glucose transporter 4 in subcutaneous and visceral adipose tissue. Markers of obesity, IR and PCOS were also measured.

Results: In PCOS patients, lipin 1β expression in both adipose depots was lower than in controls: 0.76 (0.67–0.84) vs 1.16 (0.90–1.43) for visceral and 0.91 (0.73–1.10) vs 1.30 (1.03–1.57) for s.c. depot (both P<10^–4). The difference remained significant after adjustment for body mass index (BMI) and also when comparing only lean patients with lean controls. In PCOS patients, visceral adipose lipin 1β expression correlated negatively with homeostasis model assessment–IR (r=–0.474, P=0.017), BMI (r=–0.511, P=0.009) and waist circumference (r=–0.473, P=0.017), waist circumference remaining significant (P=0.027) in multiple regression. Subcutaneous lipin 1β expression in PCOS correlated negatively with BMI, waist circumference and plasma triglycerides, and positively with high density lipoprotein-cholesterol. Subcutaneous, but not visceral lipin 1β expression, correlated positively with the studied genes.

Conclusions: Lipin 1β appears to be involved in the pathogenesis of IR in PCOS.