Subcutaneous adipose tissue zinc-α2-glycoprotein is associated with adipose tissue and whole-body insulin sensitivity

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.

Download Full-text

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass

Scientific Reports ◽

10.1038/s41598-021-94189-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Julie Abildgaard ◽

Thorkil Ploug ◽

Elaf Al-Saoudi ◽

Thomas Wagner ◽

Carsten Thomsen ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Visceral Fat ◽

Subcutaneous Adipose Tissue ◽

Immune Cell ◽

Whole Body ◽

Metabolic Dysfunction ◽

Adipocyte Hypertrophy ◽

Subcutaneous Adipose

AbstractMenopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combined this with anthropometric measurements and estimated whole-body insulin sensitivity. We found that menopause was associated with changes in adipose tissue phenotype related to metabolic dysfunction. In SAT, postmenopausal women showed adipocyte hypertrophy, increased inflammation, hypoxia and fibrosis. The postmenopausal changes in SAT was associated with increased visceral fat accumulation. In VAT, menopause was associated with adipocyte hypertrophy, immune cell infiltration and fibrosis. The postmenopausal changes in VAT phenotype was associated with decreased insulin sensitivity. Based on these findings we suggest, that menopause is associated with changes in adipose tissue phenotype related to metabolic dysfunction in both SAT and VAT. Whereas increased SAT inflammation in the context of menopause is associated with VAT accumulation, VAT morphology is related to insulin resistance.

Download Full-text

Markers Of Remodeling In Subcutaneous Adipose Tissue Are Associated With The Amount Of Abdominal Adipose Tissue, Overweight And Insulin Sensitivity In Healthy Middle Aged Men

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.06.791 ◽

2019 ◽

Vol 287 ◽

pp. e257

Author(s):

S. Åkra ◽

T.B. Opstad ◽

T.A. Aksnes ◽

I. Seljeflot

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Subcutaneous Adipose Tissue ◽

Middle Aged ◽

Abdominal Adipose Tissue ◽

Subcutaneous Adipose

Download Full-text

Inflammation and impaired adipogenesis in hypertrophic obesity in man

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00377.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. E999-E1003 ◽

Cited By ~ 162

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.

Download Full-text

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.5.e850 ◽

1992 ◽

Vol 263 (5) ◽

pp. E850-E855 ◽

Cited By ~ 13

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.

Download Full-text

Subcutaneous adipose tissue metabolic function and insulin sensitivity in people with obesity

Diabetes ◽

10.2337/db21-0160 ◽

2021 ◽

pp. db210160

Author(s):

Han-Chow E. Koh ◽

Stephan van Vliet ◽

Terri A. Pietka ◽

Gretchen A. Meyer ◽

Babak Razani ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Subcutaneous Adipose Tissue ◽

Metabolic Function ◽

Subcutaneous Adipose

Download Full-text

Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa571 ◽

2020 ◽

Vol 105 (11) ◽

Author(s):

Christoph Hoffmann ◽

Patrick Schneeweiss ◽

Elko Randrianarisoa ◽

Günter Schnauder ◽

Lisa Kappler ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Endurance Training ◽

Mitochondrial Respiration ◽

Subcutaneous Adipose Tissue ◽

Muscle Fibers ◽

Sensitivity Index ◽

Respiratory Capacity ◽

Subcutaneous Adipose

Abstract Context Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. Objective To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. Design Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). Results Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. Conclusion Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

Download Full-text

Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00358.2002 ◽

2003 ◽

Vol 284 (2) ◽

pp. E443-E448 ◽

Cited By ~ 43

Author(s):

A. S. Lihn ◽

T. Østergård ◽

B. Nyholm ◽

S. B. Pedersen ◽

B. Richelsen ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Subcutaneous Adipose Tissue ◽

Diabetic Patients ◽

Mrna Levels ◽

Type 2 Diabetic Patients ◽

Adiponectin Mrna ◽

Subcutaneous Adipose ◽

Type 2 Diabetic

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced Mvalue (4.44 vs. 6.09 mg · kg−1· min−1, P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls ( P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 μg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11–13%) but significantly in both groups ( P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin ( P < 0.05) and positively correlated with insulin sensitivity ( P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.

Download Full-text