Profiling of G-Protein Coupled Receptors in Adipose Tissue and Differentiating Adipocytes Offers a Translational Resource for Obesity/Metabolic Research

Author:

Al Mahri Saeed12,Okla Meshail34ORCID,Rashid Mamoon5,Malik Shuja Shafi1ORCID,Iqbal Jahangir6ORCID,Al Ibrahim Maria1,Dairi Ghida178,Mahmood Amer4ORCID,Muthurangan Manikandan4ORCID,Yaqinuddin Ahmed2ORCID,Mohammad Sameer1ORCID

Affiliation:

1. Experimental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh 11426, Saudi Arabia

2. College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia

3. Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11495, Saudi Arabia

4. Stem Cell Unit and Anatomy Department, College of Medicine, King Saud University, Riyadh 11495, Saudi Arabia

5. Biostatistics and Bioinformatics Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (NGHA), Riyadh 11426, Saudi Arabia

6. King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City Hospital, Ministry of National Guard Health Affairs (NGHA), Al Hasa 31982, Saudi Arabia

7. Physiology Department, College of Medicine, King Saud University, Riyadh 11362, Saudi Arabia

8. Deanship of Scientific Research, Umm Al-Qura University, Makkah 21961, Saudi Arabia

Abstract

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose metabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expression of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects and in adipocytes isolated from regular chow and high-fat fed mice were evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots, but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differentiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA sequencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. High-fat diet had a significant impact on adipocyte GPCR expression that was similar to human obesity. Finally, we report several highly expressed GPCRs with no known role in adipose biology whose expression was significantly altered during adipogenic differentiation, and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

Funder

King Abdullah International Medical Research Center

Publisher

MDPI AG

Subject

General Medicine

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