Introduction 1 2 3 4 5 6 7 2 8 2 5 R a 9 10 Methods Participants 2 2 5 2 2 2 5 1 11 Table 1 Clinical characteristics of the participants   n n Age (years) 43 ± 3 54 ± 3 2 23.0 ± 0.5 a FM (kg) 15.2 ± 0.8 a WHR 0.91 ± 0.01 a Systolic blood pressure (mmHg) 126 ± 3 137 ± 4 Diastolic blood pressure (mmHg) 77 ± 2 85 ± 3 HOMA-IR 1.8 ± 0.2 a Values are mean ± SEM a p HOMA-IR, homeostatic model assessment of insulin resistance Experimental protocol Pilot study 2 5 n 2 5 −1 −1 t t t t t t t t t t t Whole-body and SAT lipolysis study 2 5 −1 −1 −1 −1 n t t t t t t 133 12 13 Clinical methods 14 2 5 −1 −1 3 15 15 Analytical methods 2 g 16 Isotope enrichment g m z 17 Calculations The net exchange (flux) of metabolites across abdominal SAT was calculated by multiplying the arterio–venous concentration difference of metabolites by adipose tissue plasma flow. Plasma flow was calculated as ATBF×(1–packed cell volume), with packed cell volume expressed as a fraction. A positive net flux indicates net uptake from plasma, whereas a negative net flux indicates net tissue release. The expected adipose vein enrichment, in case of no glycerol uptake, was calculated as arterialised enrichment multiplied by arterialised glycerol concentration divided by the measured adipose vein enrichment. R a \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ R_{a} {\left( {\mu \operatorname{mol} \,kg^{{ - 1}} \,\min ^{{ - 1}} } \right)} = \operatorname{TTR} ^{{ - 1}} \times F $$\end{document} F −1 −1 2 5 2 5 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$ {\text{abdominal}}\,{\text{SAT}}\,{\text{total}}\,{\text{glycerol}}\,{\text{uptake = fract $ \times $ }}{\left( {{\text{glycerol}}_{{{\text{art}}}} } \right)}{\text{ $ \times $ ATBF}} $$\end{document} −1 −1 art −1 −1 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$ {\text{abdominal}}\,{\text{SAT}}\,{\text{total}}\,{\text{glycerol}}\,{\text{release = abdominal}}\,{\text{SAT}}\,{\text{net}}\,{\text{glycerol}}\,{\text{flux - abdominal}}\,{\text{SAT}}\,{\text{total}}\,{\text{glycerol}}\,{\text{uptake}}$$\end{document} Statistical analysis t p Results Characteristics 1 2 Table 2 Circulating (arterialised) metabolite levels during baseline (fasting) and isoprenaline infusion in lean and obese participants   Lean Obese n n n n TAG (μmol/l) 701 ± 66 648 ± 64 b a NEFA (μmol/l) 661 ± 41 942 ± 53 638 ± 42 a Glycerol (μmol/l) 102 ± 5 118 ± 7 106 ± 4 a R a 199 ± 12 311 ± 28 220 ± 15 391 ± 30 R a −1 −1 13.1 ± 0.9 20.9 ± 1.6 b a Glucose (mmol/l) 5.3 ± 0.1 5.4 ± 0.1 5.5 ± 0.2 5.4 ± 0.1 Insulin (pmol/l) 50 ± 4 74 ± 6 b a Values are mean ± SEM b p a p t Tracer/tracee ratio 2 5 n 1 n 2 5 Fig. 1 2 5 n Circulating metabolites 2 p 2 p p 2 R a 2 R a p 2 R a p 2 R a R a −1 −1 p 2 2 p 2 Abdominal SAT lipolysis 2 2 5 p p −1 −1 p 2 r p Fig. 2 a b 2 5 p 3 3 −1 −1 p 2 −1 −1 p 3 Table 3 Blood flow and net SAT fluxes during baseline (fasting) and isoprenaline infusion in lean and obese participants   Lean Obese n n n n −1 −1 2.2 ± 0.2 6.3 ± 1.2 a 3.6 ± 0.6 −1 −1 TAG 25 ± 8 43 ± 17 34 ± 29 113 ± 62 NEFA −780 ± 160 −2,101 ± 371 −486 ± 101 −1,824 ± 667 Glycerol −229 ± 49 −640 ± 148 −211 ± 51 −486 ± 128 Glucose 53 ± 49 −69 ± 151 −143 ± 96 −677 ± 632 Values are mean ± SEM A positive net flux indicates net uptake from plasma, whereas a negative net flux indicates net tissue release a p t Discussion The present study was designed to investigate in vivo whole-body and abdominal SAT lipolysis in obese and lean men. To our knowledge, this is the first study to show in vivo that obese participants have a blunted beta-adrenergically mediated lipolytic response per unit of adipose tissue. Methodological considerations 9 10 2 5 2 5 Glycerol uptake 2 5 9 10 18 Abdominal SAT lipolytic response to beta-adrenergic stimulation 2 4 5 6 7 2 8 19 22 7 4 23 2 24 25 26 Whole-body beta-adrenergically mediated lipolytic response R a 2 27 28 29 30 31 Conclusion The present study demonstrates in vivo that obese men have a blunted beta-adrenergically mediated lipolytic response in abdominal SAT. Therefore, a blunted lipolysis during beta-adrenergic stimulation may be an important factor in the development or maintenance of increased TAG stores and obesity.