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      Comprehensive lipidomic analysis reveals regulation of glyceride metabolism in rat visceral adipose tissue by high-altitude chronic hypoxia

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      Author(s): 1 , 2 , 3 , 4 , * ,
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      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Adipose tissue plays a central role in energy substrate homeostasis and is a key regulator of lipid flow throughout these processes. As hypoxia affects lipid metabolism in adipose tissue, we aimed to investigate the effects of high-altitude chronic hypoxia on lipid metabolism in the adipose tissue of rats using a lipidomic analysis approach. Visceral adipose tissues from rats housed in a high-altitude hypoxia environment representing 4,300 m with 14.07% oxygen (hypoxia group) and from rats housed in a low-altitude normoxia environment representing 41 m with 20.95% oxygen (normoxia group) for 8 weeks were analyzed using an ultra-performance liquid chromatography-Orbitrap mass spectrometry system. After 8 weeks, the body weight and visceral adipose tissue weight of the hypoxia group were significantly decreased compared to those of the normoxia group (p < 0.05). The area and diameter of visceral adipose cells in the hypoxia group were significantly smaller than those of visceral adipose cells in the normoxia group (p < 0.05). The results of lipidomic analysis showed a total of 21 lipid classes and 819 lipid species. The total lipid concentration of the hypoxia group was lower than that in the normoxia group (p < 0.05). Concentrations of diacylglycerols and triacylglycerols in the hypoxia group were significantly lower than those in the normoxia group (p < 0.05). Using univariate and multivariate analyses, we identified 74 lipids that were significantly altered between the normoxia and hypoxia groups. These results demonstrate that high-altitude chronic hypoxia changes the metabolism of visceral adipose glycerides, which may potentially modulate other metabolic processes.

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          Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis.

          Javier Menendez, Ruth Lupu (2007)
          There is a renewed interest in the ultimate role of fatty acid synthase (FASN)--a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids--in cancer pathogenesis. Tumour-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to necessarily accompany the natural history of most human cancers. A recent identification of cross-talk between FASN and well-established cancer-controlling networks begins to delineate the oncogenic nature of FASN-driven lipogenesis. FASN, a nearly-universal druggable target in many human carcinomas and their precursor lesions, offers new therapeutic opportunities for metabolically treating and preventing cancer.
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            Lipid landscapes and pipelines in membrane homeostasis.

            Joost Holthuis, Anant K. Menon (2014)
            The lipid composition of cellular organelles is tailored to suit their specialized tasks. A fundamental transition in the lipid landscape divides the secretory pathway in early and late membrane territories, allowing an adaptation from biogenic to barrier functions. Defending the contrasting features of these territories against erosion by vesicular traffic poses a major logistical problem. To this end, cells evolved a network of lipid composition sensors and pipelines along which lipids are moved by non-vesicular mechanisms. We review recent insights into the molecular basis of this regulatory network and consider examples in which malfunction of its components leads to system failure and disease.
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              Reduced Adipose Tissue Oxygenation in Human Obesity

              Magdalena Pasarica, Olga Sereda, Leanne Redman … (2009)
              OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity. CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity.
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                Author and article information

                Contributors
                Hong Liang: Role: Writing – original draft
                Jun Yan: Role: Methodology
                Kang Song:
                ORCID: https://orcid.org/0000-0002-0926-9044
                Role: Writing – review & editing
                Xiaoyan Hui: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS One
                Journal ID (publisher-id): plos
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 6 May 2022
                Publication date Collection: 2022
                Volume: 17
                Issue: 5
                Electronic Location Identifier: e0267513
                Affiliations
                [1 ] Department of Basic Medical Sciences, Medical College, Qinghai University, Xining, PR, China
                [2 ] Cardiovascular Medicine Department, Xuzhou Medical University affiliated Hospital, Xuzhou, PR China
                [3 ] Endocrinology Department, Qinghai Provincial People’s Hospital, Xining, PR, China
                [4 ] Qinghai University affiliated Provincial People’s Hospital, Xining, PR, China
                The Chinese University of Hong Kong, HONG KONG
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-0926-9044
                Article
                Publisher ID: PONE-D-21-40070
                DOI: 10.1371/journal.pone.0267513
                PMC ID: 9075645
                PubMed ID: 35522648
                SO-VID: 26614e14-96c9-477e-b126-700c4a60b477
                Copyright © © 2022 Liang et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 21 December 2021
                Date accepted : 10 April 2022
                Page count
                Figures: 6, Tables: 0, Pages: 14
                Funding
                Funded by: Qinghai University Doctoral Research Initiation project
                Funded by: Qinghai Province high-end talent innovation project
                Qinghai University Doctoral Research Initiation project and Qinghai Province high-end talent innovation project.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Lipids
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Medical Hypoxia
                Subject: Biology and Life Sciences
                Subject: Molecular Biology
                Subject: Macromolecular Structure Analysis
                Subject: Lipid Analysis
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Adipose Tissue
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Adipose Tissue
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Lipids
                Subject: Lipid Metabolism
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Metabolism
                Subject: Lipid Metabolism
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Hypoxia
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Adipose Tissue
                Subject: Adipocytes
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Adipose Tissue
                Subject: Adipocytes
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Connective Tissue Cells
                Subject: Adipocytes
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Connective Tissue Cells
                Subject: Adipocytes
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Connective Tissue Cells
                Subject: Adipocytes
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Parameters
                Subject: Body Weight
                Custom metadata
                Data Availability All relevant data are within the manuscript and its Supporting Information files.

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