Adipocyte Lipases and Defect of Lipolysis in Human Obesity
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Figures
- FIG. 1.
Selectivity of BAY for inhibition of HSL. A: Concentration-response inhibition by BAY of purified human HSL (hHSL) or rat HSL (rHSL), pancreatic lipase (PL), lipoprotein lipase (LPL), and monoglyceride lipase (MGL) enzymatic activities (n = 3). B: BAY (10−6 mol/l) inhibition of triglyceride hydrolase activity in Cos7 cells expressing human HSL or human ATGL (n = 3). C: Concentration-response inhibition by BAY of mouse adipose tissue extract triglyceride hydrolase activity (n = 3). D: BAY (10−6 mol/l) inhibition of triglyceride hydrolase activity in wild-type and HSL-null mouse adipose tissue extracts (n = 4).
- FIG. 2.
Lipolysis in isolated adipocytes from wild-type and HSL-null mice. A: Glycerol release (n = 5). Concentration-response curves of isoprenaline were performed without BAY (squares), with 10−8 mol/l BAY (diamonds), or with 10−6 mol/l BAY (triangles). B: Glycerol release (n = 3). Concentration-response inhibition of BAY was measured on lipolysis induced by 10−4 mol/l isoprenaline. C: FFA release (n = 3). Concentration-response inhibition of BAY was measured on lipolysis induced by 10−4 mol/l isoprenaline.
- FIG. 3.
Effect of BAY on human fat cell lipolysis. A: Antilipolytic effects of BAY (▪, 10−10 mol/l; □, 10−7 mol/l), insulin (•, 10−8 mol/l), and prostaglandin E2 (▵, 10−5 mol/l) on isoprenaline-induced glycerol release. ○, dose-response curve of isoprenaline without antilipolytic agents (n = 4). B: Effect of BAY on basal (□), isoprenaline-induced (○, 10−7 mol/l), and atrial natriuretic peptide–induced (▴, 10−7 mol/l) glycerol release (n = 3). C: Inhibition by BAY (10−5 mol/l) of basal, isoprenaline-induced (Iso, 10−7 mol/l), and atrial natriuretic peptide–induced (ANP, 10−7 mol/l) glycerol and FFA release (n = 6). D: BAY (10−6 mol/l) inhibition of triglyceride (triolein) and diglyceride (MOME) hydrolase activity in human adipose tissue extracts (n = 4).
- FIG. 4.
HSL and ATGL gene expression in human adipose tissue. HSL and ATGL mRNA levels were quantified by reverse transcription-quantitative PCR and normalized with 18S rRNA levels. A: HSL and ATGL mRNA levels in isolated adipocytes and stromavascular fraction (SVF) from human adipose tissue (n = 6). B: Expression of HSL, ATGL, and peroxisome proliferator–activated receptor γ (PPARγ) mRNA during human preadipocyte differentiation (n = 5). C: Relationship between HSL and ATGL mRNA levels in subcutaneous adipose tissue from 80 obese women. D: Relationship between HSL and ATGL mRNA variation during a hypocaloric diet in subcutaneous adipose tissue from 24 obese women. HSL and ATGL mRNA levels were measured before and after a 10-week hypocaloric diet. The variations are calculated as follows for each individual: (mRNA level after the diet − mRNA level before the diet)/mRNA level before the diet.
- FIG. 5.
Lipolysis, leptin secretion, and HSL expression in mature adipocytes and differentiated preadipocytes from obese and lean subjects. A: Glycerol and leptin release in isolated mature adipocytes from 42 lean and 81 obese subjects. B: Glycerol and leptin release in preadipocytes differentiated in primary culture from 42 lean and 81 obese subjects. C: Protein expression of HSL and β2-adrenoceptor (β2-AR) in differentiated human preadipocytes from 14 obese and 7 lean subjects determined by Western blot analysis.
- FIG. 6.
Model for stimulatory pathways in human adipose tissue lipolysis. For the sake of clarity, important nonenzymatic modulators of the lipolytic process such as perilipins are not shown. AC, adenylyl cyclase; AR, adrenoceptor; DG, diglyceride; FA, fatty acid; GC, guanylate cyclase; Gs, stimulatory G protein; MG, monoglyceride; MGL, monoglyceride lipase; NPRA, natriuretic peptide receptor A; PKA, protein kinase A; PKG, protein kinase G; TG, triglyceride.
