Dataset Information

The effects of mild intermittent hypoxia exposure on the abdominal subcutaneous adipose tissue proteome in overweight and obese men: A first-in-human randomized, single-blind, cross-over study

ABSTRACT: Adipose tissue (AT) oxygen tension (pO2) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome. We performed a randomized, single-blind, cross-over study to investigate the effects of seven consecutive days of MIH (FiO2 15%, 3x2h/d) compared to normoxia (FiO2 21%) exposure, on the AT proteome in overweight/obese men. AT insulin sensitivity was determined by a two-step hyperinsulinemic-euglycemic clamp, and abdominal subcutaneous AT biopsies were collected (n=11) under normoxic, fasting conditions following both exposure regimens. AT proteins were isolated and quantified using liquid chromatography-mass spectrometry. After correction for blood contamination, 1022 AT protein IDs were identified, of which 123 were differentially expressed following MIH (p < 0.05). These proteins were involved in redox systems, cell-adhesion, actin cytoskeleton organization, extracellular matrix composition and energy metabolism. We demonstrate for the first time that MIH exposure impacts the AT proteome. Moreover, differential AT TMOD3 expression is related to changes in AT insulin sensitivity, thereby linking MIH-induced effects on the AT proteome to metabolic changes in overweight/obese humans.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Subcutaneous Preadipocyte

SUBMITTER: freek bouwman

LAB HEAD: Freek Bouwman

PROVIDER: PXD029213 | Pride | 2022-02-16

REPOSITORIES: Pride

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Publications

The Effects of Mild Intermittent Hypoxia Exposure on the Abdominal Subcutaneous Adipose Tissue Proteome in Overweight and Obese Men: A First-in-Human Randomized, Single-Blind, and Cross-Over Study.

Van Meijel Rens L J RLJ Wang Ping P Bouwman Freek F Blaak Ellen E EE Mariman Edwin C M ECM Goossens Gijs H GH

Frontiers in physiology 20220104

Adipose tissue (AT) oxygen tension (pO<sub>2</sub>) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome. We performed a randomized, single-blind, and cross-over study to investigate the effects of seven consecutive days of MIH (FiO<sub>2</ ...[more]

PMID: 35058800

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Project description:The identification of novel tumor-specific markers may improve understanding of melanoma progression and prognostic accuracy. Whole genome expression profiling of 46 primary melanomas, 12 metastases, and 16 normal skin samples using Affymetrix U133 PLUS 2.0 array generated gene lists including both known and new melanoma genes. The molecular genetic alterations contributing to the pathogenesis of melanoma are incompletely defined and few independent prognostic features have been identified beyond the pathologic characteristics of the primary tumor. Early stage melanoma is frequently curable, in contrast to the inferior prognosis of melanomas with regional lymph nodes involvement and the incurability of distant metastatic disease. The identification of novel tumor-specific markers may improve our understanding of melanoma progression and prognostic accuracy. To find differentially expressed genes that can distinguish melanoma from normal tissue, we performed a whole genome expression profiling of 46 primary melanoma samples, 12 regional or distant metastases, and 16 normal skin samples using Affymetrix U133 2.0 Plus array. Our study generated lists of differentially expressed genes in melanoma and identified novel prognostic marker HMGA2. It is a novel, highly overexpressed melanoma gene associated with poor prognosis. The overexpression of HMGA2 is strongly associated with regional and distant metastases and serves as an independent predictor of disease-free survival and overall survival in melanoma. Melanoma samples were obtained through an IRB-approved protocol using informed consent at the University of Michigan Multidisciplinary Melanoma Clinic. A portion of pigmented lesions clinically suspicious for melanoma and known melanoma were sampled by punch biopsy at the time of excision. The punch biopsy was bisected; half was sent to for clinical diagnosis and the other half along with adjacent normal skin when available immediately snap-frozen in liquid nitrogen. Snap-frozen tissue was embedded in OCT (TissueTek) followed by frozen sectioning and H&E slide preparation. The slides were evaluated by dermatopathologist who identified areas with greater than 70% tumor cellularity, which were sampled for RNA extraction. Primary melanomas and melanoma metastases were derived from different patients. Metastatic samples included lymph nodes (n=8), subcutaneous soft tissue (n=2), spleen (n=1), and small intestine (n=1).

Dataset Information

The effects of mild intermittent hypoxia exposure on the abdominal subcutaneous adipose tissue proteome in overweight and obese men: A first-in-human randomized, single-blind, cross-over study

Publications

The Effects of Mild Intermittent Hypoxia Exposure on the Abdominal Subcutaneous Adipose Tissue Proteome in Overweight and Obese Men: A First-in-Human Randomized, Single-Blind, and Cross-Over Study.

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