Substrate utilization and thermogenic responses to β-adrenergic stimulation in obese subjects with NIDDM

Abstract

OBJECTIVE: This study intended to investigate disturbances in b-adrenergically-mediated substrate utilization and thermogenesis in obese subjects with mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the b-agonist isoproterenol (ISO) was administered in increasing doses of 6, 12, and 24 ngakg FFM .min, each dose for 30 min. SUBJECTS: Nine healthy lean males (CON, 50.6 AE 2.4 y, % body fat: 16.0 AE 1.8) and 10 obese subjects with NIDDM (51.8 AE 2.4 y, % body fat 34.1 AE 1.9). RESULTS: Basal non esteri®ed fatty acid concentrations (NEFA) and basal fat oxidation (absolute or expressed per unit fat free mass, FFM) were signi®cantly higher in NIDDM as compared to CON, whereas basal carbohydrate (CHO) oxidation was signi®cantly lower. The ISO-induced increase in NEFA-concentrations was blunted in NIDDM (D at 24 ngakg FFM .min: CON: 717 AE 59 mmolal vs NIDDM: 358 AE 97 mmolal, P`0.01). The non-protein respiratory exchange ratio (RER) did not change in NIDDM and signi®cantly decreased in CON during ISO-infusion (P`0.05), re¯ecting the tendency towards a blunted increase in fat oxidation in NIDDM (D fat ox at 24 ng; CON: 0.025 AE 0.005 gamin vs NIDDM 0.016 AE 0.007 gamin). The ISO-induced thermogenic response was comparable in NIDDM and CON (at 24 ng %increase above baseline: CON: 16.8 AE 2.2% vs NIDDM: 14.7 AE 0.9%). At all time points, there were no signi®cant differences in circulating ISO and noradrenaline concentrations. Basal adrenaline (A) concentrations and A concentrations during ISO-infusion were signi®cantly lower in NIDDM (basal A; CON: 64 AE 15 pgaml vs NIDDM: 25 AE 2 pgaml, P`0.001). CONCLUSION: There appear to be deviations in b-adrenoceptor mediated fat utilization and adrenal medulla function in obesity-associated NIDDM. The impairments in sympathetically mediated fat utilization have previously been observed in`simple' obese subjects, indicating that these disturbances are con®ned to the obese state per se.

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

“…It should be mentioned that there are major differences in catecholamine-induced lipolysis between depots (subcutaneous vs visceral and gluteofemoral) and also gender differences in body fat distribution. [43][44][45] Our data indicate that variability in codon 16 of the ADRB2 gene may contribute to a reduced in vivo b-adrenoceptor-mediated lipolysis and fat oxidation, [1][2][3][4] indicating that these blunted responses may be important primary factors in obesity.…”

“…In vivo studies have shown that the development or maintenance of increased adipose tissue stores might be promoted by a blunted lipolytic response and fat oxidation after b-adrenergic stimulation or exercise in obese or obese type 2 diabetic subjects. [1][2][3][4] This blunted b-adrenoceptor-mediated lipolysis and fat oxidation persisted after weight reduction, indicating that this disturbance may be an early, even primary factor, in the development or maintenance of increased adipose stores. 1 There are indications that the blunted b-adrenergically mediated lipolysis in obesity may be related to an impaired function or a reduced number of adipocyte beta-2 (b 2 ) adrenoceptors.…”

The effect of exercise training on β-adrenergic stimulation of fat metabolism in obese men

“…The present study was designed to investigate whether the impaired sympathetically mediated fat oxidation, reported in obese subjects in several studies, 1,5,6,30 could be improved by exercise training independent of changes in body mass and body composition. However, the obese subjects who participated in the present study did not appear to have a blunted b-adrenergically mediated fat oxidation.…”

“…This effect was in agreement with that previously found in lean. 1,5,6,30 Apparently the effect of b-adrenergic stimulation on fat oxidation is variable in obese subjects. Unfortunately no data were available to compare the level of physical ®tness of the obese subjects in our study with the obese subjects in the studies mentioned above.…”

“…However, it is possible that the obese subjects in the present study, who volunteered in an exercise training program, were better trained than the average obese subject participating in other non-training studies. 1,5,6,30 It is known in the lean that exercise-trained subjects have an increased b-adrenergic lipolytic response in vitro compared to sedentary subjects. 17,19 ± 22,31 Moreover, also variations in habitual energy expenditure seem to play a role in the difference between high and low responders of b-adrenergic adipocyte lipolysis.…”