Increased Aquaporin-7 Expression Is Associated with Changes in Rat Brown Adipose Tissue Whitening in Obesity: Impact of Cold Exposure and Bariatric Surgery

Author:

Frühbeck Gema1234ORCID,Méndez-Giménez Leire1,Becerril Sara123ORCID,Ramírez Beatriz123,Hernández-Pardos Ana Wenting1,Cienfuegos Javier A.5,Valentí Víctor235,Moncada Rafael236,Catalán Victoria123ORCID,Gómez-Ambrosi Javier123ORCID,da Silva Inês V.7ORCID,Soveral Graça7ORCID,Rodríguez Amaia123ORCID

Affiliation:

1. Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain

2. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain

3. Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain

4. Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain

5. Department of Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain

6. Department of Anesthesia, Clínica Universidad de Navarra, 31008 Pamplona, Spain

7. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-004 Lisbon, Portugal

Abstract

Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white-like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2, Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4 °C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2, Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.

Funder

Fondo de Investigación Sanitaria-FEDER

Instituto de Salud Carlos III

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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