scholarly journals Visceral Adipose Tissue Phospholipid Signature of Insulin Sensitivity and Obesity

2021 ◽  
Author(s):  
Magalí Palau-Rodriguez ◽  
Anna Marco-Ramell ◽  
Patricia Casas-Agustench ◽  
Sara Tulipani ◽  
Antonio Miñarro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Visceral Adipose Tissue ◽  
Tissue Phospholipid ◽  
Visceral Adipose

scholarly journals LMO3 reprograms visceral adipocyte metabolism during obesity

2021 ◽  
Author(s):  
Gabriel Wagner ◽  
Anna Fenzl ◽  
Josefine Lindroos-Christensen ◽  
Elisa Einwallner ◽  
Julia Husa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Visceral Adipose Tissue ◽  
Tissue Expansion ◽  
Oxidative Capacity ◽  
Glut4 Translocation ◽  
Mitochondrial Oxidative Capacity ◽  
Visceral Adipose

Abstract Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. Key messages LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.

Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome

2017 ◽  
Vol 125 (08) ◽  
pp. 522-529 ◽  
Author(s):  
Danijela Milutinović ◽  
Marina Nikolić ◽  
Nataša Veličković ◽  
Ana Djordjevic ◽  
Biljana Bursać ◽  
...  
Keyword(s):  
Animal Model ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Abdominal Obesity ◽  
Visceral Adipose Tissue ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Visceral Adipose

AbstractPolycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.

Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women

2008 ◽  
Vol 33 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Jennifer L. Kuk ◽  
Katherine Kilpatrick ◽  
Lance E. Davidson ◽  
Robert Hudson ◽  
Robert Ross
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Visceral Adipose Tissue ◽  
Skeletal Muscle Mass ◽  
Whole Body ◽  
Men And Women ◽  
Visceral Adipose

The relationship between skeletal muscle mass, visceral adipose tissue, insulin sensitivity, and glucose tolerance was examined in 214 overweight or obese, but otherwise healthy, men (n = 98) and women (n = 116) who participated in various exercise and (or) weight-loss intervention studies. Subjects had a 75 g oral glucose tolerance test and (or) insulin sensitivity measures by a 3 h hyperinsulinemic–euglycemic clamp technique. Whole-body skeletal muscle mass and visceral adipose tissue were measured using a multi-slice magnetic resonance imaging protocol. Total body skeletal muscle mass was not associated with any measure of glucose metabolism in men or women (p > 0.10). These observations remained independent of age and total adiposity. Conversely, visceral adipose tissue was a significant predictor of various measures of glucose metabolism in both men and women with or without control for age and (or) total body fat (p < 0.05). Although skeletal muscle is a primary site for glucose uptake and deposition, these findings suggest that unlike visceral adipose tissue, whole-body skeletal muscle mass per se is not associated with either glucose tolerance or insulin sensitivity in overweight and obese men and women.

Visceral adipose tissue impairs insulin secretion and insulin sensitivity but not energy expenditure in obesity

Metabolism ◽  
1997 ◽  
Vol 46 (2) ◽  
pp. 123-129 ◽  
Author(s):  
C. Macor ◽  
A. Ruggeri ◽  
P. Mazzonetto ◽  
G. Federspil ◽  
C. Cobelli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Visceral Adipose Tissue ◽  
Visceral Adipose

scholarly journals What Are the Physical Characteristics Associated with a Normal Metabolic Profile Despite a High Level of Obesity in Postmenopausal Women?1

2001 ◽  
Vol 86 (3) ◽  
pp. 1020-1025 ◽  
Author(s):  
Martin Brochu ◽  
André Tchernof ◽  
Isabelle J. Dionne ◽  
Cynthia K. Sites ◽  
Georgia H. Eltabbakh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Postmenopausal Women ◽  
Lean Body Mass ◽  
Body Mass ◽  
Body Fat ◽  
Visceral Adipose Tissue ◽  
Oral Glucose ◽  
Age Related ◽  
Visceral Adipose

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean ± sd, 58.0± 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 ± 2.6 mg/min·kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 ± 1.1 mg/min·kg lean body mass). Despite comparable total body fatness between groups (45.2 ± 5.3% vs. 44.8 ± 6.6%; P = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 ± 53 vs. 211 ± 85 cm2; P &lt; 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 ± 126 vs. 442 ± 144 cm2; P = NS), total fat mass (38.1 ± 10.6 vs. 40.0 ± 11.8 kg), muscle attenuation (42.2± 2.6 vs. 43.6 ± 4.8 Houndsfield units), and physical activity energy expenditure (1060 ± 323 vs. 1045 ± 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P values ranging between 0.01–0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P &lt; 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (&lt;20 yr old) compared with 29% of the MAO subjects (P = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r2 = 0.35; P &lt; 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.

scholarly journals Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue

2005 ◽  
Vol 288 (5) ◽  
pp. E930-E934 ◽  
Author(s):  
Neda Rasouli ◽  
Ulrika Raue ◽  
Leslie M. Miles ◽  
Tong Lu ◽  
Gina B. Di Gregorio ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Lipid Oxidation ◽  
Visceral Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Oxidative Enzymes ◽  
Muscle Lipid ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Patients with insulin resistance often manifest increased intramyocellular lipid (IMCL) along with increased visceral adipose tissue. This study was designed to determine whether the insulin sensitizer drugs pioglitazone and metformin would improve glucose intolerance and insulin sensitivity by decreasing IMCL. In this study, 23 generally healthy subjects with impaired glucose tolerance were randomized to receive either pioglitazone 45 mg/day or metformin 2,000 mg/day for 10 wk. Before and after treatment, we measured insulin sensitivity and abdominal subcutaneous and visceral adipose tissue with CT scanning. In addition, muscle biopsies were performed for measurement of IMCL and muscle oxidative enzymes. After treatment with pioglitazone, 2-h glucose fell from 9.6 mmol/l (172 mg/dl) to 6.1 mmol/l (119 mg/dl), whereas there was no change in 2-h glucose with metformin. With pioglitazone treatment, there was a 65% increase in insulin sensitivity along with a 34% decrease in IMCL (both P ≤ 0.002). This decrease in IMCL was not due to increased muscle lipid oxidation, as there were no changes in muscle lipid oxidative enzymes. However, pioglitazone resulted in a 2.6-kg weight gain along with a significant decrease in the visceral-to-subcutaneous adipose tissue ratio. In contrast, metformin treatment resulted in no change in insulin sensitivity, IMCL, oxidative enzymes, or adipose tissue volumes. Pioglitazone improved glucose tolerance and insulin sensitivity by reducing IMCL. This reduction in IMCL was not due to an increase in muscle lipid oxidation but to a diversion of lipid from ectopic sites into subcutaneous adipose tissue.

scholarly journals ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Kristen L. Mittelsteadt ◽  
Erika T. Hayes ◽  
Daniel J. Campbell
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Insulin Sensitivity ◽  
Visceral Adipose Tissue ◽  
Cell Accumulation ◽  
Elevated Expression ◽  
Phosphoinositide 3 Kinase ◽  
And Function ◽  
Adipose Inflammation ◽  
Visceral Adipose

A unique population of Foxp3+ regulatory T cells (TRs) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. Inducible T cell co-stimulator (ICOS) is highly expressed on effector (e)TRs that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream phosphoinositide 3-kinase (PI3K) signaling in limiting the abundance, VAT-associated phenotype, and function of TRs specifically in VAT. Icos−/− mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TRs to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of a high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function.

scholarly journals ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue

2020 ◽  
Author(s):  
Kristen L. Mittelsteadt ◽  
Daniel J. Campbell
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Visceral Adipose Tissue ◽  
High Fat Diet ◽  
Costimulatory Molecule ◽  
Cell Accumulation ◽  
Elevated Expression ◽  
And Function ◽  
Adipose Inflammation ◽  
Visceral Adipose

AbstractA unique population of Foxp3+ regulatory T cells (TR) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. The costimulatory molecule ICOS is highly expressed on effector (e)TR that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream PI3K signaling in limiting the abundance, VAT-associated phenotype, and function of TR specifically in VAT. Icos−/− mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TR to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function.

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