Characterization of the inflammatory and metabolic profile of adipose tissue in a mouse model of chronic hypoxia

Abstract

In both obesity and chronic obstructive pulmonary disease (COPD), altered oxygen tension in adipose tissue (AT) has been suggested to evoke AT dysfunction, subsequently contributing to metabolic complications. Studying the effects of chronic hypoxia on AT function will add to our understanding of the complex pathophysiology of alterations in AT inflammation, metabolism, and mass observed in both obesity and COPD. This study investigated the inflammatory and metabolic profile of AT after chronic hypoxia. Fifty-two-week-old C57Bl/6J mice were exposed to chronic hypoxia (8% O2) or normoxia for 21 days, after which AT and plasma were collected. Adipocyte size, AT gene expression of inflammatory and metabolic genes, AT macrophage density, and circulating adipokine concentrations were measured. Food intake and body weight decreased upon initiation of hypoxia. However, whereas food intake normalized after 10 days, lower body weight persisted. Chronic hypoxia markedly reduced AT mass and adipocyte size. AT macrophage density and expression of Emr1, Ccl2, Lep, and Tnf were decreased, whereas Serpine1 and Adipoq expression levels were increased after chronic hypoxia. Concomitantly, chronic hypoxia increased AT expression of regulators of oxidative metabolism and markers of mitochondrial function and lipolysis. Circulating IL-6 and PAI-1 concentrations were increased, and leptin concentration was decreased after chronic hypoxia. Chronic hypoxia is associated with decreased rather than increased AT inflammation, and markedly decreased fat mass and adipocyte size. Furthermore, our data indicate that chronic hypoxia is accompanied by significant alterations in AT metabolic gene expression, pointing toward an enhanced AT metabolic rate.

Resveratrol Attenuates Intermittent Hypoxia-Induced Macrophage Migration to Visceral White Adipose Tissue and Insulin Resistance in Male Mice

“…First, we have implemented an IH experimental paradigm that provides highly reproducible findings and, most importantly, mimics frequently encountered patterns of episodic hypoxia occurring in diseases such as OSA (15). In this context, the initial prominent reductions in food consumption and overall diminished nutrient intake exhibited by IH-exposed mice is similar to that previously reported by us (15) as well as by others (42) and may reflect relative leptin receptor resistance induced by IH in the context of an overall catabolic state (43). Notably, Resv treatment improved IH-mediated deceleration in weight gain during the duration of the experiments, suggesting that the both central and peripheral metabolic and orexigenic pathways modulated by IH are affected by this compound, an effect that is not apparent during normoxic conditions.…”

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

“…However, analysis of blood cytokines profile [e.g. Tumor Necrosis Factor-a, Interleukin (IL)-1b, adiponectin, chemokine (C-C motif) ligand 5, monocyte chemoattractant protein-1] did not reveal any marked alteration with hypoxia, with the exception of an increase in IL-6 content [120]. From this study, cytokines do no seems to be implicated in hypoxia-induced muscle atrophy, although further work is required to decipher their influence on muscle phenotype.…”

Proinflammatory cytokines differentially regulate adipocyte mitochondrial metabolism, oxidative stress, and dynamics

“…It also plays a vital role in communicating to the brain and other tissues as to the energy status of the entire organism and hence, can influence feeding behavior and energy utilization (9, 21, 52). Low-grade chronic inflammation of adipose tissue has been characterized as a hallmark of obesity and insulin resistance (14,17,50). Current models of obesitylinked adipose inflammation include leukocyte infiltration, increased levels of proinflammatory cytokines such as monocyte chemotactic protein-1, tumor necrosis factor-␣ (TNF␣), interleukin-6 (IL-6), and interleukin-1␤ (IL-1␤) and increased oxidative stress (14, 23).…”