Leptin production during early starvation in lean and obese women

2000 ◽  
Vol 278 (2) ◽  
pp. E280-E284 ◽  
Author(s):  
Samuel Klein ◽  
Jeffrey F. Horowitz ◽  
Michael Landt ◽  
Stephen J. Goodrick ◽  
Vidya Mohamed-Ali ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Upper Body ◽  
Whole Body ◽  
Obese Women ◽  
Local Production ◽  
Abdominal Adipose Tissue ◽  
Arterial Concentration ◽  
Relative Decline ◽  
Plasma Leptin ◽  
Subcutaneous Adipose

We evaluated abdominal adipose tissue leptin production during short-term fasting in nine lean [body mass index (BMI) 21 ± 1 kg/m2] and nine upper body obese (BMI 36 ± 1 kg/m2) women. Leptin kinetics were determined by arteriovenous balance across abdominal subcutaneous adipose tissue at 14 and 22 h of fasting. At 14 h of fasting, net leptin release from abdominal adipose tissue in obese subjects (10.9 ± 1.9 ng ⋅ 100 g tissue ⋅ − 1 ⋅ min− 1) was not significantly greater than the values observed in the lean group (7.6 ± 2.1 ng ⋅ 100 g− 1 ⋅ min− 1). Estimated whole body leptin production was approximately fivefold greater in obese (6.97 ± 1.18 μg/min) than lean subjects (1.25 ± 0.28 μg/min) ( P < 0.005). At 22 h of fasting, leptin production rates decreased in both lean and obese groups (to 3.10 ± 1.31 and 10.5 ± 2.3 ng ⋅ 100 g adipose tissue− 1 ⋅ min− 1, respectively). However, the relative declines in both arterial leptin concentration and local leptin production in obese women (arterial concentration 13.8 ± 4.4%, local production 10.0 ± 12.3%) were less ( P < 0.05 for both) than the relative decline in lean women (arterial concentration 39.0 ± 5.5%, local production 56.9 ± 13.0%). This study demonstrates that decreased leptin production accounts for the decline in plasma leptin concentration observed after fasting. However, compared with lean women, the fasting-induced decline in leptin production is blunted in women with upper body obesity. Differences in leptin production during fasting may be responsible for differences in the neuroendocrine response to fasting previously observed in lean and obese women.

Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women

2000 ◽  
Vol 278 (6) ◽  
pp. E1144-E1152 ◽  
Author(s):  
Jeffrey F. Horowitz ◽  
Samuel Klein
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Lipolytic Activity ◽  
Fat Free Mass ◽  
Upper Body ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Obese Women ◽  
Epinephrine Infusion ◽  
Subcutaneous Adipose

We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 ± 1 kg/m2] and 10 upper body obese (UBO) women (BMI: 38 ± 1 kg/m2; waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 μg ⋅ kg fat-free mass−1 ⋅ min−1) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (Ra) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and 133Xe clearance methods. Basal whole body FFA Ra and glycerol Ra were both greater ( P < 0.05) in obese (449 ± 31 and 220 ± 12 μmol/min, respectively) compared with lean subjects (323 ± 44 and 167 ± 21 μmol/min, respectively). Epinephrine infusion significantly increased FFA Ra and glycerol Ra in lean (71 ± 21 and 122 ± 52%, respectively; P < 0.05) but not obese subjects (7 ± 6 and 39 ± 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.

scholarly journals Whole body, adipose tissue, and forearm norepinephrine kinetics in lean and obese women

1998 ◽  
Vol 275 (5) ◽  
pp. E830-E834 ◽  
Author(s):  
Simon W. Coppack ◽  
Jeffrey F. Horowitz ◽  
Deanna S. Paramore ◽  
Philip E. Cryer ◽  
Henry D. Royal ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Fat Free Mass ◽  
Upper Body ◽  
Whole Body ◽  
Obese Women ◽  
Abdominal Vein ◽  
Subcutaneous Abdominal Adipose Tissue ◽  
Forearm Vein

We evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE) kinetics in seven lean (body mass index 21.3 ± 0.5 kg/m2) and six upper body obese (body mass index 36.4 ± 0.4 kg/m2) women who were matched on fat-free mass. NE kinetics were determined by infusing [3H]NE and obtaining blood samples from a radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. Mean systemic NE spillover tended to be higher in obese (2.82 ± 0.49 nmol/min) than in lean (2.53 ± 0.40 nmol/min) subjects, but the differences were not statistically significant. Adipose tissue and forearm NE spillover rates into plasma were greater in lean (0.91 ± 0.08 pmol ⋅ 100 g tissue−1 ⋅ min−1and 1.01 ± 0.09 pmol ⋅ 100 ml tissue−1 ⋅ min−1, respectively) than in obese (0.26 ± 0.05 pmol ⋅ 100 g tissue−1 ⋅ min−1and 0.58 ± 0.11 pmol ⋅ 100 ml tissue−1 ⋅ min−1, respectively) subjects ( P < 0.01). These results demonstrate that adipose tissue is an active site for NE metabolism in humans. Adipose tissue NE spillover is considerably lower in obese than in lean women, which may contribute to the lower rate of lipolysis per kilogram of fat mass observed in obesity.

Effect of short-term fasting on lipid kinetics in lean and obese women

1999 ◽  
Vol 276 (2) ◽  
pp. E278-E284 ◽  
Author(s):  
Jeffrey F. Horowitz ◽  
Simon W. Coppack ◽  
Deanna Paramore ◽  
Philip E. Cryer ◽  
Guohong Zhao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Upper Body ◽  
Whole Body ◽  
Obese Women ◽  
Short Term ◽  
Nervous System Activity ◽  
Percent Increase ◽  
Obese Subjects ◽  
Adipose Tissue Lipolysis ◽  
Percent Decline

We evaluated whole body and regional adipose tissue lipid kinetics and norepinephrine (NE) spillover during brief fasting in six lean [body mass index (BMI) 21 ± 1 kg/m2] and six upper-body obese (UBO; BMI 36 ± 1 kg/m2) women. At 14 h of fasting, abdominal adipose tissue glycerol and free fatty acid (FFA) release rates were lower ( P = 0.07), but whole body glycerol and FFA rates of appearance (Ra) were greater ( P < 0.05) in obese than in lean subjects. At 22 h of fasting, glycerol and FFA Ra increased less in obese (19.8 ± 7.0 and 87.1 ± 30.3 μmol/min, respectively) than in lean (44.2 ± 6.6 and 137.4 ± 30.4 μmol/min, respectively; P < 0.05) women. The percent increase in glycerol Ra correlated closely with the percent decline in plasma insulin in both groups ( r 2 = 0.85; P < 0.05). Whole body NE spillover declined in lean ( P < 0.05) but not obese subjects with continued fasting, whereas regional adipose tissue NE spillover did not change in either group. We conclude that, compared with lean women, in UBO women 1) basal adipose tissue lipolysis is lower, but whole body lipid kinetics is higher because of their greater fat mass; 2) the increase in lipolysis during fasting is blunted because of an attenuated decline in circulating insulin; and 3) downregulation of whole body sympathetic nervous system activity is impaired during fasting.

scholarly journals Effects of Physiological Hypercortisolemia on the Regulation of Lipolysis in Subcutaneous Adipose Tissue1

1998 ◽  
Vol 83 (2) ◽  
pp. 626-631 ◽  
Author(s):  
Jaswinder S. Samra ◽  
Mo L. Clark ◽  
Sandy M. Humphreys ◽  
Ian A. MacDonald ◽  
Peter A. Bannister ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Sodium Succinate ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Constant Infusion ◽  
Nonesterified Fatty Acid ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
Subcutaneous Adipose

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused iv to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 ± 100 vs. 335± 25 nmol/L; P &lt; 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the sc adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of[ 1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P &lt; 0.01) and blood glycerol concentrations (P &lt; 0.05), with an increase in systemic glycerol appearance (P &lt; 0.05). However, in sc abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P &lt; 0.05) and reduced NEFA efflux (P &lt; 0.05). This reduction was attributable to decreased intracellular lipolysis (P &lt; 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P &lt; 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

Inflammation and impaired adipogenesis in hypertrophic obesity in man

2009 ◽  
Vol 297 (5) ◽  
pp. E999-E1003 ◽  
Author(s):  
Birgit Gustafson ◽  
Silvia Gogg ◽  
Shahram Hedjazifar ◽  
Lachmi Jenndahl ◽  
Ann Hammarstedt ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Preadipocyte Differentiation ◽  
Metabolic Complications ◽  
Adipose Cell ◽  
Subcutaneous Adipose ◽  
Adipose Cell Size

Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNFα, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

1992 ◽  
Vol 263 (5) ◽  
pp. E850-E855 ◽  
Author(s):  
L. Simonsen ◽  
J. Bulow ◽  
J. Madsen ◽  
N. J. Christensen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Epinephrine Infusion ◽  
Basal Period ◽  
Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

scholarly journals Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women

Diabetologia ◽  
2008 ◽  
Vol 51 (12) ◽  
pp. 2303-2308 ◽  
Author(s):  
T. McLaughlin ◽  
A. Deng ◽  
O. Gonzales ◽  
M. Aillaud ◽  
G. Yee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Obese Women ◽  
Modest Increase ◽  
Subcutaneous Adipose

scholarly journals Subcutaneous adipose tissue free fatty acid uptake measured using positron emission tomography and adipose biopsies in humans

2019 ◽  
Vol 317 (2) ◽  
pp. E194-E199
Author(s):  
Yanli Cao ◽  
Nicola Gathaiya ◽  
Qiaojun Han ◽  
Bradley J. Kemp ◽  
Michael D. Jensen
Keyword(s):  
Positron Emission Tomography ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Subcutaneous Fat ◽  
Emission Tomography ◽  
Abdominal Adipose Tissue ◽  
Positron Emission ◽  
Uptake Rates ◽  
Palmitate Uptake ◽  
Subcutaneous Adipose

Positron emission tomography (PET) radiopharmaceuticals can noninvasively measure free fatty acid (FFA) uptake into adipose tissue. We studied 29 volunteers to test whether abdominal and femoral subcutaneous adipose tissue FFA uptake measured using [1-11C]palmitate PET agrees with FFA storage rates measured using an intravenous bolus of [1-14C]palmitate and adipose biopsies. The dynamic left ventricular cavity PET images combined with blood sample radioactivity corrected for the 11CO2 content were used to create the blood time activity curve (TAC), and the constant ( Ki) was determined using Patlak analysis of the TACs generated for regions of interest in abdominal subcutaneous fat. These data were used to calculate palmitate uptake rates in abdominal subcutaneous adipose tissue (µmol·kg−1·min−1). Immediately after the dynamic imaging, a static image of the thigh was taken to measure the standardized uptake value (SUV) in thigh adipose tissue, which was scaled to each participant’s abdominal adipose tissue SUV to calculate thigh adipose palmitate uptake rates. Abdominal adipose palmitate uptake using PET [1-11C]palmitate was correlated with, but significantly ( P < 0.001) greater than, FFA storage measured using [1-14C]palmitate and adipose biopsy. Thigh adipose palmitate measured using PET calculation was positively correlated ( R2 = 0.44, P < 0.0001) with and not different from the biopsy approach. The relative differences between PET measured abdominal subcutaneous adipose tissue palmitate uptake and biopsy-measured palmitate storage were positively correlated ( P = 0.03) with abdominal subcutaneous fat. We conclude that abdominal adipose tissue FFA uptake measured using PET does not equate to adipose FFA storage measured using biopsy techniques.

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