Depot-Specific Expression of Lipolytic Genes in Human Adipose Tissues

Abstract

Aim: Adipocyte lipolysis is mediated by a family of triglyceride (TG) lipases consisting of hormonesensitive lipase (LIPE), adipose triglyceride lipase (PNPLA2) and carboxylesterase 1 (CES1); however, little is known about the relationship between the expression of each gene in different depots and TG lipase activity or obesity Method: We measured both mRNA expression levels of the lipolytic enzymes (LIPE, PNPLA2 and CES1) and TG lipase activities of biopsy samples obtained from subcutaneous, omental and mesenteric adipose tissues of 34 patients who underwent abdominal surgery. The results were correlated with clinical parameters: adiposity measures, parameters for insulin resistance and plasma lipid levels. Results: PNPLA2 mRNA levels were slightly higher in omental fat than subcutaneous fat. Cytosolic TG lipase activities were positively correlated with the mRNA levels of CES1 in subcutaneous fat and mesenteric fat, while they were correlated with those of PNPLA2 in omental fat. The mRNA levels of LIPE were negatively correlated with various measures of adiposity in subcutaneous fat. The mRNA levels of CES1 were positively correlated with various measures of adiposity, particularly those estimated by CT in the three depots; they were also positively correlated with plasma LDL-cholesterol levels in omental fat. In contrast, the mRNA levels of PNPLA2 were not significantly associated with adiposity. Conclusions: The positive correlations of the expression of CES1 with cytosolic TG lipase activities as well as with adiposity suggest that CES1 is involved in lipolysis, thereby contributing to the development of obesity-associated phenotypes. On the other hand, the expression of LIPE is negatively correlated with adiposity. These distinct regulatory patterns of lipolytic genes may underlie the complex phenotypes associated with human obesity.

Pathophysiology of Human Visceral Obesity: An Update

“…Most studies seem to show that lipolytic rates are lower in mesenteric adipocytes compared with subcutaneous fat cells in the basal state (134, 166, 581), although mesenteric cells, much like omental cells, were found to be more responsive to ␤-adrenergic stimulation compared with other fat depots (166, 581). Cytosolic and microsomal triglyceride lipase activities were reported to be lower in mesenteric than in subcutaneous adipose tissue (388). Mesenteric fat was also shown to have higher basal lipolysis but blunted isoproterenol responsiveness compared with other depots in diabetic subjects (632).…”

Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel

“…CYP2C9, CYP2C19 and CYP3A4) may also play role as it leads to reduced bioactivation [49]. Some recent studies also showed that expression level of CES1, which governs clopidogrel elimination from the body, was significantly elevated in obese subjects and could be reversed by diet-induced weight loss [50, 51], indicating that the impact of obesity in clopidogrel response may be associated with multiple mechanisms. However, the link between obesity and treatment outcome seems inconclusive and an “obesity paradox” has been reported from several clinical investigations, where patients with lower BMI (normal and underweight) had an increased risk of bleeding as well as elevated clinical outcome including death and MI than the obese ones, due to the fact that, in these studies, higher BMI was associated with a trend towards male patients with younger ages, who usually show the tendency of seeking for medical care earlier and more aggressive initial management compared to older subjects [16, 42, 45, 52, 53].…”

Carboxylesterase 1 Gene Duplication and mRNA Expression in Adipose Tissue Are Linked to Obesity and Metabolic Function

“…So far, the expression of CES1 mRNA in T2DM has not been examined. However, it has been suggested that the expression of CES1 mRNA in human adipose tissue is correlated with measures of adiposity and metabolic function including waist circumference, homeostasis model assessment-insulin resistance (HOMA-IR), triglyceride level, and plasma insulin level [12]–[14]. In contrast, findings of a relationship between CES1 mRNA level and other measures of metabolic function such as body-mass index (BMI) and total cholesterol level are inconsistent, possibly reflecting limited statistical power [13], [14] and inclusion of study participants with malignant diseases [14].…”