Sandra L. H. Schiffelers

The effect of an increased free fatty acid concentration on thermogenesis and substrate oxidation in obese and lean men

OBJECTIVE: To examine whether a certain increase in plasma free fatty acid (FFA) concentration leads to similar increases in lipid oxidation and energy expenditure in obese and lean men.DESIGN: The study protocol consisted of a 30 min baseline period after which subjects received an i.v. bolus of 1000 IE heparin. Then consecutive infusions of 4.9, 9.8 and 19.6 μl/kg fat-free mass (FFM)·min of a lipid heparin mixture were started, each infusion for 30 min.SUBJECTS: Eleven obese and 13 lean men with a mean body mass index (BMI) of 34.2±1.0 (±s.e.m.) and 23.9±0.5 kg/m2 and age 46.0±1.0 and 42.6±1.5 y, respectively.MEASUREMENTS: Energy expenditure, respiratory exchange ratio (RER) and carbohydrate and lipid oxidation were continuously measured by indirect calorimetry. At the end of each infusion period, a blood sample was taken for FFA, glycerol, insulin, β-hydroxybutyrate, noradrenaline and adrenaline determination.RESULTS: At baseline, plasma FFA levels were comparable in both groups. Lipid heparin infusion increased plasma FFA concentration by 301±47 μmol/l and 332±27 μmol/l in obese and lean men. Energy expenditure increased similarly in obese and lean men (0.34±0.08 vs 0.40±0.08 kJ/min, NS) during lipid heparin infusion, whereas RER decreased similarly in both groups. Lipid oxidation rates were comparable at baseline and increased similarly in obese and lean men (19±5 vs 13±4 mg/min, NS). Baseline plasma insulin levels were higher in the obese, but did not change during lipid heparin infusion. Plasma β-hydroxybutyrate concentrations were similar at baseline, but increased significantly less in the obese during lipid heparin infusion. Baseline noradrenaline and adrenaline concentrations did not differ significantly between groups. During lipid heparin infusion, plasma noradrenaline levels decreased significantly, but plasma adrenaline levels remained unchanged in both groups.CONCLUSION: A certain increase in plasma FFA concentration leads to similar increases in lipid oxidation and energy expenditure in obese and lean men. The accumulation of fat in obese subjects may therefore be more likely to be due to a defect in adipose tissue lipolysis than a defect in lipid oxidation.

In vivo β3-Adrenergic Stimulation of Human Thermogenesis and Lipid Use

To investigate the role of the human β3‐adrenergic receptor in in vivo isoproterenol (INN, isoprenaline)‐induced thermogenesis and lipid use.

Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation

Background and aims:Obesity is associated with a blunted β-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the β 2-adrenoceptor gene (ADRB2) and exon 10 of the G protein β 3-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation.Design and methods:Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1–48.4 kg/m2) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective β-agonist isoprenaline (ISO).Results:In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation.Conclusion:These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo β-adrenoceptor-mediated lipolysis and fat oxidation during β-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene–gender interactions.

Inhibition of lipolysis reduces β1-adrenoceptor—mediated thermogenesis in man☆

The purpose of the study was to investigate whether the increase in energy expenditure and lipid oxidation during beta1-adrenergic stimulation is caused by the concomitant increase in lipolysis. Twelve healthy male subjects participated in three trials: no-LIP/-, inhibition of lipolysis by pretreatment with acipimox followed by saline infusion; -/BETA, no pretreatment, with dobutamine infusion to stimulate beta1-adrenoceptors; and no-LIP/BETA, pretreatment with acipimox followed by dobutamine infusion. Inhibition of lipolysis did not affect baseline energy expenditure, but decreased lipid oxidation and increased carbohydrate oxidation. Energy expenditure and lipid oxidation increased significantly during beta1-adrenergic stimulation, but this increase was significantly smaller when lipolysis was inhibited ([baseline v infusion period] energy expenditure: -/BETA, 5.15 +/- 0.16 v 6.11 +/- 0.26 kJ/min, P < .001; no-LIP/BETA, 5.28 +/- 0.17 v 5.71 +/- 0.19 kJ/min, P < .01; lipid oxidation: -/BETA, 0.059 +/- 0.004 v 0.073 +/- 0.006 g/min, P < .01; no-LIP/BETA, 0.034 +/- 0.005 v 0.039 +/- 0.006 g/min, P < .05). Baseline plasma glycerol and nonesterified fatty acid (NEFA) concentrations decreased after inhibition of lipolysis. Glycerol and NEFA increased significantly during beta1-adrenergic stimulation alone (glycerol, 65.0 +/- 5.3 v 117.0 +/- 10.9 micromol/L; NEFA, 362 +/- 24 v 954 /- 89 micromol/L; both P < .001). Concomitant administration of acipimox prevented a substantial part of the increase in lipolysis during beta1-adrenergic stimulation, but the increase in plasma glycerol and NEFA remained significant (glycerol, 40.4 +/- 2.2 v 44.8 +/- 2.2 micromol/L; NEFA, 118 +/- 18 v 160 +/- 19 micromol/L; both P < .05). In conclusion, a reduced availability of plasma NEFA was associated with a reduced increase in energy expenditure and lipid oxidation during beta1-adrenergic stimulation in man.

Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men

OBJECTIVE: β-Adrenoceptor-mediated whole-body lipolysis is impaired in obesity. This study investigated whether local adipocyte β-adrenergic sensitivity and changes in nutritive blood flow in subcutaneous abdominal adipose tissue contribute to this impaired response.METHODS: Three microdialysis probes were placed in the subcutaneous abdominal adipose tissue of eight obese and nine lean men. Each probe was perfused with either 0.1, 1 and 10 μM isoprenaline; 1, 10 and 100 μM dobutamine or 1, 10 and 100 μM salbutamol, each dose for 45 min.RESULTS: At baseline, interstitial glycerol concentrations and ethanol out/in ratios were comparable between groups. During nonselective β-, β1- and β2-adrenergic stimulation, interstitial glycerol concentrations increased and ethanol out/in ratios decreased similarly in obese and lean men.CONCLUSION: The lipolytic and nutritive blood flow response to β1- β2- and nonselective β-adrenergic stimulation in situ is comparable in lean and obese male subjects. The present data suggest that a blunted β-adrenergic sensitivity of the fat cell and an impaired local nutritive blood flow response do not contribute to the previously reported diminished whole-body β-adrenoceptor-mediated lipolytic response in obese males.