Amino acid metabolism in human subcutaneous adipose tissue in vivo

1991 ◽  
Vol 80 (5) ◽  
pp. 471-474 ◽  
Author(s):  
K. N. Frayn ◽  
K. Khan ◽  
S. W. Coppack ◽  
M. Elia

1. Arteriovenous differences for alanine, glutamate and glutamine were measured across subcutaneous adipose tissue and forearm muscle in normal subjects. 2. After an overnight fast, adipose tissue showed net production of alanine and glutamine and uptake of glutamate in each of 11 subjects. 3. In seven subjects, adipose tissue blood flow was measured and the measurements were continued for 6 h after eating a mixed meal. The pattern of amino acid metabolism across the adipose tissue was remarkably little disturbed after the meal, except for a short period of apparent uptake of alanine as the concentration of that amino acid rose. 4. The pattern of amino acid metabolism across adipose tissue was qualitatively similar to that across the forearm, although it differed quantitatively in that glutamate uptake was more prominent (compared with glutamine release) in the adipose tissue. 5. The rates of alanine and glutamine release observed suggest that adipose tissue may play a substantial role in the whole-body production of these amino acids.

GeroScience ◽  
2021 ◽  
Author(s):  
Haihui Zhuang ◽  
Sira Karvinen ◽  
Timo Törmäkangas ◽  
Xiaobo Zhang ◽  
Xiaowei Ojanen ◽  
...  

AbstractAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial β-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.


2002 ◽  
Vol 282 (4) ◽  
pp. E931-E936 ◽  
Author(s):  
Bruce W. Patterson ◽  
Jeffrey F. Horowitz ◽  
Guoyao Wu ◽  
Malcolm Watford ◽  
Simon W. Coppack ◽  
...  

The effect of obesity on regional skeletal muscle and adipose tissue amino acid metabolism is not known. We evaluated systemic and regional (forearm and abdominal subcutaneous adipose tissue) amino acid metabolism, by use of a combination of stable isotope tracer and arteriovenous balance methods, in five lean women [body mass index (BMI) <25 kg/m2] and five women with abdominal obesity (BMI 35.0–39.9 kg/m2; waist circumference >100 cm) who were matched on fat-free mass (FFM). All subjects were studied at 22 h of fasting to ensure that the subjects were in net protein breakdown during this early phase of starvation. Leucine rate of appearance in plasma (an index of whole body proteolysis), expressed per unit of FFM, was not significantly different between lean and obese groups (2.05 ± 0.18 and 2.34 ± 0.04 μmol · kg FFM−1 · min−1, respectively). However, the rate of leucine release from forearm and adipose tissues in obese women (24.0 ± 4.8 and 16.6 ± 6.5 nmol · 100 g−1 · min−1, respectively) was lower than in lean women (66.8 ± 10.6 and 38.6 ± 7.0 nmol · 100 g−1 · min−1, respectively; P < 0.05). Approximately 5–10% of total whole body leucine release into plasma was derived from adipose tissue in lean and obese women. The results of this study demonstrate that the rate of release of amino acids per unit of forearm and adipose tissue at 22 h of fasting is lower in women with abdominal obesity than in lean women, which may help obese women decrease body protein losses during fasting. In addition, adipose tissue is a quantitatively important site for proteolysis in both lean and obese subjects.


2020 ◽  
Author(s):  
Haihui Zhuang ◽  
Sira Karvinen ◽  
Xiaobo Zhang ◽  
Xiaowei Ojanen ◽  
Timo Törmakangas ◽  
...  

ABSTRACTAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) platform. Interaction of aerobic capacity and aging was studied via regression analysis. Our results showed at young age, metabolites linked to amino acid metabolism differed in serum and muscle with aerobic capacity, whereas no difference were observed in WAT. In aged animals, most prominent changes in metabolites occurred in WAT. Aerobic capacity and aging interactively affected seven metabolites linked to energy metabolism. Our results support previous findings that high aerobic capacity is associated with more efficient amino acid metabolism in muscle. While impaired branched chain amino acids (BCAAs) and fatty acid metabolism in the muscle may associate to the high risk of metabolic disorders and shorter lifespan previously observed in LCRs. The interactive effects of aging and aerobic capacity on energy metabolism-related metabolites were largely driven by HCRs, reflecting the importance of inherited aerobic capacity in the aging process. Our results highlight that dysfunctional mitochondrial β-oxidation in WAT may be one key mechanism related to aging.


2000 ◽  
Vol 279 (2) ◽  
pp. E376-E385 ◽  
Author(s):  
Bente Stallknecht ◽  
Jens J. Larsen ◽  
Kari J. Mikines ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
...  

Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men [insulin infusion rates: 10,000 ( step I), 20,000 ( step II), and 150,000 ( step III) μU · min−1 · m−2]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle (glucose only). Adipose tissue blood flow was measured by 133Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration difference was increased in T during the clamp but not in S subjects in both adipose tissue and muscle [adipose tissue: step I ( n = 8), 0.48 ± 0.18 mM (T), 0.23 ± 0.11 mM (S); step II ( n = 8), 0.19 ± 0.09 (T), −0.09 ± 0.24 (S); step III( n = 5), 0.47 ± 0.24 (T), 0.06 ± 0.28 (S); (T: P < 0.001, S: P > 0.05); muscle: step I ( n = 4), 1.40 ± 0.46 (T), 0.31 ± 0.21 (S); step II ( n = 4), 1.14 ± 0.54 (T), −0.08 ± 0.14 (S); step III( n = 4), 1.23 ± 0.34 (T), 0.24 ± 0.09 (S); (T: P < 0.01, S: P > 0.05)]. Interstitial glycerol concentration decreased faster in T than in S subjects [half-time: T, 44 ± 9 min ( n = 7); S, 102 ± 23 min ( n = 5); P < 0.05]. In conclusion, training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis in subcutaneous adipose tissue. Insulin per se does not influence subcutaneous adipose tissue blood flow.


2000 ◽  
Vol 278 (6) ◽  
pp. E1144-E1152 ◽  
Author(s):  
Jeffrey F. Horowitz ◽  
Samuel Klein

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.


2009 ◽  
Vol 297 (5) ◽  
pp. E999-E1003 ◽  
Author(s):  
Birgit Gustafson ◽  
Silvia Gogg ◽  
Shahram Hedjazifar ◽  
Lachmi Jenndahl ◽  
Ann Hammarstedt ◽  
...  

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.


1992 ◽  
Vol 263 (5) ◽  
pp. E850-E855 ◽  
Author(s):  
L. Simonsen ◽  
J. Bulow ◽  
J. Madsen ◽  
N. J. Christensen

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.


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