Fat redistribution following suction lipectomy: defense of body fat and patterns of restoration.

No randomized studies in humans have examined whether fat returns after removal or where it returns. We undertook a prospective, randomized-controlled trial of suction lipectomy in nonobese women to determine if adipose tissue (AT) is defended and if so, the anatomic pattern of redistribution. Healthy women with disproportionate AT depots (lower abdomen, hips, or thighs) were enrolled. Baseline body composition measurements included dual-energy X-ray absorptiometry (DXA) (a priori primary outcome), abdominal/limb circumferences, subcutaneous skinfold thickness, and magnetic resonance imaging (MRI) (torso/thighs). Participants (n = 32; 36 ± 1 year) were randomized to small-volume liposuction (n = 14, mean BMI: 24 ± 2 kg/m(2)) or control (n=18, mean BMI: 25 ± 2) following baseline. Surgery group participants underwent liposuction within 2-4 weeks. Identical measurements were repeated at 6 weeks, 6 months, and 1 year later. Participants agreed not to make lifestyle changes while enrolled. Between-group differences were adjusted for baseline level of the outcome variable. After 6 weeks, percent body fat (%BF) by DXA was decreased by 2.1% in the lipectomy group and by 0.28% in the control group (adjusted difference (AD): -1.82%; 95% confidence interval (CI): -2.79% to -0.85%; P = 0.0002). This difference was smaller at 6 months, and by 1 year was no longer significant (0.59% (control) vs. -0.41% (lipectomy); AD: -1.00%; CI: -2.65 to 0.64; P = 0.23). AT reaccumulated differently across various sites. After 1 year the thigh region remained reduced (0.77% (control) vs. -1.83% (lipectomy); AD: -2.59%; CI: -3.91 to -1.28; P = 0.0001), but AT reaccumulated in the abdominal region (0.64% (control) vs. 0.42% (lipectomy); AD: -0.22; CI: -2.35 to 1.91; P = 0.84). Following suction lipectomy, BF was restored and redistributed from the thigh to the abdomen.

Leptin increases skeletal muscle lipoprotein lipase and postprandial lipid metabolism in mice.

The ability of leptin to preserve lean tissue during weight loss may be in part due to differences in nutrient partitioning. Because lipoprotein lipase (LPL) plays a key role in partitioning lipid nutrients, this study was conducted to test the hypothesis that leptin would modify the tissue-specific regulation of LPL and result in increased lipid oxidation and decreased storage. The effects of daily intraperitoneal leptin injections (2 mg/kg body weight) over 2 weeks on LPL activity and postprandial lipid metabolism were tested in both wild-type (WT), leptin-deficient ob/ob obese mice and mice pair fed to the leptin-treated mice. On the experimental day, mice were given food by gavage, blood was drawn periodically, and adipose tissue and skeletal muscle were harvested for measurements of LPL activity at 240 minutes. After 2 weeks of leptin administration, skeletal muscle LPL (SMLPL) activity was increased in leptin-treated compared with pair-fed (P = .012) and WT (P = .002) mice. There was no effect of leptin or pair feeding on postprandial adipose tissue LPL activity. In ob/ob mice, leptin treatment normalized the decrease in postprandial free fatty acid concentration (P = .066). Leptin had no effect on either the area under the triglyceride (TG) excursion or the integrated area under the TG excursion in WT mice. In ob/ob mice, however, the TG excursion was lower in the leptin-treated than the pair-fed mice by area under the TG excursion (P = .012) and was lower than in the WT mice by integrated area under the TG excursion (P = .027). As expected, 2 weeks of leptin treatment decreased body weight in both the WT and ob/ob mice (-2.6% and -10.4%, respectively). Leptin treatment increased SMLPL, an effect that may have contributed to the leptin-induced weight loss. The leptin-induced decreased postprandial TG excursion in ob/ob mice suggests that leptin acts to augment clearance of postprandial TG-rich lipoprotein lipid and that this increase may in part be secondary to the increased activity of SMLPL. The trend for decreased postprandial free fatty acid may indicate that leptin decreases adipose tissue lipid stores without increasing lipolysis.

The metabolic syndrome.

The "metabolic syndrome" (MetS) is a clustering of components that reflect overnutrition, sedentary lifestyles, and resultant excess adiposity. The MetS includes the clustering of abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure and is associated with other comorbidities including the prothrombotic state, proinflammatory state, nonalcoholic fatty liver disease, and reproductive disorders. Because the MetS is a cluster of different conditions, and not a single disease, the development of multiple concurrent definitions has resulted. The prevalence of the MetS is increasing to epidemic proportions not only in the United States and the remainder of the urbanized world but also in developing nations. Most studies show that the MetS is associated with an approximate doubling of cardiovascular disease risk and a 5-fold increased risk for incident type 2 diabetes mellitus. Although it is unclear whether there is a unifying pathophysiological mechanism resulting in the MetS, abdominal adiposity and insulin resistance appear to be central to the MetS and its individual components. Lifestyle modification and weight loss should, therefore, be at the core of treating or preventing the MetS and its components. In addition, there is a general consensus that other cardiac risk factors should be aggressively managed in individuals with the MetS. Finally, in 2008 the MetS is an evolving concept that continues to be data driven and evidence based with revisions forthcoming.

Increased thermogenic responsiveness to intravenous beta-adrenergic stimulation in habitually exercising humans is not related to skeletal muscle beta2-adrenergic receptor density.

Habitually exercising adults demonstrate greater thermogenic responsiveness to beta-adrenergic receptor (beta-AR) stimulation compared with their sedentary peers, but the molecular mechanisms involved are unknown. To determine the possible role of increased beta-AR density, we studied 32 healthy adults: 17 habitual aerobic exercisers (age 45 +/- 5 years, 11 males) and 15 sedentary (49 +/- 5 years, 7 males). Maximal oxygen uptake (43.7 +/- 2.5 versus 31.6 +/- 2.9 ml kg(-1) min(-1), P = 0.002, mean +/- S.E.M.) and vastus lateralis muscle maximal citrate synthase activity (1.70 +/- 0.36 versus 0.58 +/- 0.11 micromol min(-1) g(-1), P = 0.008) were higher in the habitually exercising subjects. Resting energy expenditure (EE) adjusted for fat-free mass (FFM) was similar in the habitually exercising (5903 +/- 280 kJ day(-1)) and sedentary adults (6054 +/- 289 kJ day(-1), P = 0.43). The percentage increase in EE (DeltaEE%; indirect calorimetry, ventilated hood) above resting EE in response to beta-AR stimulation (intravenous isoproterenol at 6, 12 and 24 ng (kg FFM)(-1) min(-1)) was greater (7.1 +/- 1.2, 13.7 +/- 1.0, 20.7 +/- 1.3 versus 5.9 +/- 0.9, 9.9 +/- 1.4, 15.9 +/- 1.70%, respectively, P = 0.04), and the dose of isoproterenol required to increase EE by 10% above resting EE was lower (8.2 +/- 1.5 versus 17.1 +/- 4.1 ng (kg FFM)(-1) min(-1), P = 0.03) in the habitually exercising adults. In contrast, vastus lateralis muscle beta(2)-AR density was similar in the habitually exercising and sedentary subjects (7.46 +/- 0.29 versus 7.44 +/- 0.60 fmol (mg dry weight muscle)(-1), P = 0.98), and was not related to DeltaEE% (r = 0.02, P = 0.94) or to the isoproterenol dose required to increase EE by 10% above resting EE (r = -0.06, P = 0.76). These findings indicate that increased beta(2)-AR density is not a mechanism contributing to the greater thermogenic responsiveness to beta-AR stimulation in adult humans who regularly perform aerobic exercise.

Thermic effect of food and beta-adrenergic thermogenic responsiveness in habitually exercising and sedentary healthy adult humans.

The thermic effect of food (TEF) is an important physiological determinant of total daily energy expenditure (EE) and energy balance. TEF is believed to be mediated in part by sympathetic nervous system activation and consequent beta-adrenergic receptor (beta-AR) stimulation of metabolism. TEF is greater in habitually exercising than in sedentary adults, despite similar postprandial sympathetic nervous system activation. We determined whether augmented TEF in habitually exercising adults is associated with enhanced peripheral thermogenic responsiveness to beta-AR stimulation. In separate experiments in 22 sedentary and 29 habitually exercising adults, we measured the increase in EE (indirect calorimetry, ventilated hood) during beta-AR stimulation (intravenous isoproterenol: 6, 12, and 24 ng x kg fat-free mass(-1) x min(-1)) and EE before and after a liquid meal (40% of resting EE; 53% carbohydrate, 32% fat, 15% protein). The increase in EE during incremental isoproterenol administration was greater (P = 0.01) in habitual exercisers (0.34 +/- 0.03, 0.54 +/- 0.04, 0.81 +/- 0.05 kJ/min; means +/- SE) than in sedentary adults (0.26 +/- 0.03, 0.40 +/- 0.03, 0.64 +/- 0.04 kJ/min). The area under the TEF response curve was also greater (P = 0.04) in habitual exercisers (160 +/- 9 kJ) than in sedentary adults (130 +/- 11 kJ) and was positively related to beta-AR thermogenic responsiveness (r = 0.32, P = 0.02). We conclude that TEF is related to beta-AR thermogenic responsiveness and that the greater TEF in habitual exercisers is attributable in part to their augmented beta-AR thermogenic responsiveness. Our results also suggest that peripheral thermogenic responsiveness to beta-AR stimulation is a physiological determinant of TEF and hence energy balance in healthy adult humans.

Thermogenic responsiveness to nonspecific beta-adrenergic stimulation is not related to genetic variation in codon 16 of the beta2-adrenergic receptor.

Stimulation of beta-adrenergic receptors (beta-AR) by the sympathetic nervous system (SNS) modulates energy expenditure (EE), but substantial interindividual variability is observed. We determined whether the thermogenic response to beta-AR stimulation is related to genetic variation in codon 16 of the beta(2)-AR, a biologically important beta-AR polymorphism, and whether differences in SNS activity (i.e., the stimulus for agonist-promoted downregulation) are involved. The increase in EE (DeltaEE, indirect calorimetry, ventilated hood) above resting EE in response to nonspecific beta-AR stimulation [iv isoproterenol: 6, 12, and 24 ng/kg fat-free mass (FFM)/min] was measured in 46 healthy adult humans [Arg16Arg: 9 male, 7 female, 48 +/- 5 yr; Arg16Gly: 11 male, 4 female, 53 +/- 5 yr; Gly16Gly: 3 male, 12 female, 48 +/- 5 yr (means +/- SE)]. Neither FFM-adjusted baseline resting EE (P = 0.83) nor the dose of isoproterenol required to increase EE 10% above resting (P = 0.87) differed among the three groups (Arg16Arg: 5,409 +/- 209 kJ/day, 11.2 +/- 2.1 ng x kg FFM(-1) x min(-1); Arg16Gly: 5,367 +/- 272 kJ/day, 11.1 +/- 2.1 ng x kg FFM(-1) x min(-1); Gly16Gly: 5,305 +/- 159 kJ/day, 10.5 +/- 1.4 ng x kg FFM(-1) x min(-1)). Consistent with this, muscle sympathetic nerve activity and plasma norepinephrine concentrations were not different among the groups. Group differences in sex composition did not influence the results. Our findings indicate that the thermogenic response to nonspecific beta-AR stimulation, an important mechanistic component of overall beta-AR modulation of EE, is not related to this beta(2)-AR polymorphism in healthy humans. This may be explained in part by a lack of association between this gene variant and tonic SNS activity.

Thermogenic responsiveness to beta-adrenergic stimulation is augmented in exercising versus sedentary adults: role of oxidative stress.

Beta-adrenergic receptor (beta-AR) modulation of resting and postprandial energy expenditure (EE) is augmented in regularly exercising compared with sedentary adults, but the underlying physiological mechanisms are unknown. Differences in thermogenic responsiveness to beta-AR stimulation, perhaps secondary to reactive oxygen species (ROS) bioactivity, may be involved. To determine habitual exercise-related differences in beta-AR thermogenic responsiveness and the possible influence of ROS, we measured the percentage increase in EE (DeltaEE%; indirect calorimetry, ventilated hood method) above resting EE in response to non-specific beta-AR stimulation (intravenous isoproterenol (isoprenaline): 6, 12 and 24 ng (kg fat-free mass)-1 min-1) in 25 sedentary (11 males; 51+/-4 years; body mass index 25.0+/-0.8 kg m-2, maximal oxygen uptake 29+/-1 ml kg-1 min-1 (mean+/-s.e.m.)) and 14 habitually aerobic exercising (9 males, 46+/-6 years, 23.1+/-0.7 kg m-2, 44+/-3 ml kg-1 min-1) healthy adults under normal (control) conditions and during acute intravenous administration of a potent antioxidant, ascorbic acid (vitamin C; 0.04 g (kg fat-free mass)-1). DeltaEE% was greater (P=0.02) in the habitually exercising (8.6+/-1.2, 12.9+/-1.2, 20.0+/-1.4) versus sedentary (6.3+/-0.7, 10.4+/-0.8, 16.0+/-1.0) adults. Ascorbic acid increased (P=0.01) DeltaEE% only in the sedentary adults (to 9.5+/-0.9, 12.4+/-0.7, 18.5+/-0.8), abolishing baseline group differences. DeltaEE% was not related to the amount of body fat, sex, or any other baseline characteristic. Thermogenic responsiveness to beta-AR stimulation is augmented in habitually exercising adults. The mechanism is ascorbic acid dependent, suggesting that it may be linked to decreased ROS bioactivity. Our findings advance a novel mechanism by which habitual physical activity may modulate EE in humans, with potential implications for energy balance and body weight control.