TY - JOUR
T1 - Adipose tissue macrophage populations and inflammation are associated with systemic inflammation and insulin resistance in obesity
AU - Kunz, Hawley E.
AU - Hart, Corey R.
AU - Gries, Kevin J.
AU - Parvizi, Mojtaba
AU - Laurenti, Marcello
AU - Man, Chiara Dalla
AU - Moore, Natalie
AU - Zhang, Xiaoyan
AU - Ryan, Zachary
AU - Polley, Eric C.
AU - Jensen, Michael D.
AU - Vella, Adrian
AU - Lanza, Ian R.
N1 - Publisher Copyright:
Copyright © 2021 the American Physiological Society.
PY - 2021/7
Y1 - 2021/7
N2 - Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 nondiabetic adults across a range of body mass indexes (BMI 20.5–45.8 kg/m2). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (SI) and b cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, SI, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced SI, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-a (TNFa) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFa and CRP were negatively associated with SI, and circulating concentrations of TNFa and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.
AB - Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 nondiabetic adults across a range of body mass indexes (BMI 20.5–45.8 kg/m2). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (SI) and b cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, SI, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced SI, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-a (TNFa) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFa and CRP were negatively associated with SI, and circulating concentrations of TNFa and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.
KW - Adipose tissue resident macrophages
KW - Inflammation
KW - Insulin sensitivity
KW - Mitochondria
KW - Obesity
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U2 - 10.1152/AJPENDO.00070.2021
DO - 10.1152/AJPENDO.00070.2021
M3 - Article
C2 - 33998291
AN - SCOPUS:85111077217
SN - 0193-1849
VL - 321
SP - E105-E121
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 1
ER -