Mboat4, also known as ghrelin O-acyl transferase (GOAT), is a crucial enzyme. It catalyzes the post-translational octanoylation of Ser-3 residue of ghrelin, a 28-residue peptide hormone produced by stomach P/D1 cells. This modification is essential for ghrelin to bind to its receptor in target tissues. Ghrelin is involved in multiple physiological processes such as regulating food intake, growth hormone secretion from the pituitary, and inhibiting insulin secretion from the pancreas, highlighting the biological importance of Mboat4 in these associated pathways [1,6,7,8,9].

Some research indicates Mboat4 may be involved in lipid metabolism as gene-educational attainment interactions identified it as part of novel lipid loci, suggesting its role in adipose biology [2]. In addition, in Japanese patients with schizophrenia, the mRNA expression of Mboat4 was significantly increased, potentially reflecting the mechanisms of the disease [3]. Also, in silico studies identified pathogenic SNPs in Mboat4, suggesting it could be an anti-obesity target as it catalyzes ghrelin acylation which is related to prominent ghrelin activity [4]. In Alzheimer's disease patients, the methylation rate of Mboat4 CpG 2 was lower and its mRNA expression was higher, which may be a neuroprotective biomarker [5].

In conclusion, Mboat4 is essential for ghrelin activation and thus for various physiological functions related to metabolism and hormone regulation. Studies on Mboat4 in different disease conditions such as schizophrenia, Alzheimer's disease, and obesity-related research contribute to understanding its role in these pathologies, potentially providing new directions for therapeutic interventions.

References:

1. Murzinski, Emily S, Saha, Ishika, Ding, Hui, Tontonoz, Peter, Harran, Patrick G. 2021. In Search of Small Molecules That Selectively Inhibit MBOAT4. In Molecules (Basel, Switzerland), 26, . doi:10.3390/molecules26247599. https://pubmed.ncbi.nlm.nih.gov/34946685/

2. de las Fuentes, Lisa, Schwander, Karen L, Brown, Michael R, Rotter, Jerome I, Fornage, Myriam. 2023. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci. In Frontiers in genetics, 14, 1235337. doi:10.3389/fgene.2023.1235337. https://pubmed.ncbi.nlm.nih.gov/38028628/

3. Nakata, Shunsuke, Yoshino, Yuta, Okita, Mitsuo, Iga, Jun-Ichi, Ueno, Shu-Ichi. 2018. Differential expression of the ghrelin-related mRNAs GHS-R1a, GHS-R1b, and MBOAT4 in Japanese patients with schizophrenia. In Psychiatry research, 272, 334-339. doi:10.1016/j.psychres.2018.12.135. https://pubmed.ncbi.nlm.nih.gov/30597386/

4. Azmi, Muhammad Bilal, Sehgal, Sheikh Arslan, Asif, Uzma, Ahmed, Syed Danish Haseen, Qureshi, Shamim Akhtar. 2023. Genetic insights into obesity: in silico identification of pathogenic SNPs in MBOAT4 gene and their structural molecular dynamics consequences. In Journal of biomolecular structure & dynamics, 42, 13074-13090. doi:10.1080/07391102.2023.2274970. https://pubmed.ncbi.nlm.nih.gov/37921712/

5. Yoshino, Yuta, Funahashi, Yu, Nakata, Shunsuke, Iga, Jun-Ichi, Ueno, Shu-Ichi. 2018. Ghrelin cascade changes in the peripheral blood of Japanese patients with Alzheimer's disease. In Journal of psychiatric research, 107, 79-85. doi:10.1016/j.jpsychires.2018.10.011. https://pubmed.ncbi.nlm.nih.gov/30366284/

6. Sato, Takahiro, Ida, Takanori, Nakamura, Yuki, Kangawa, Kenji, Kojima, Masayasu. 2013. Physiological roles of ghrelin on obesity. In Obesity research & clinical practice, 8, e405-13. doi:10.1016/j.orcp.2013.10.002. https://pubmed.ncbi.nlm.nih.gov/25263830/

7. Taylor, Martin S, Hwang, Yousang, Hsiao, Po-Yuan, Boeke, Jef D, Cole, Philip A. . Ghrelin O-acyltransferase assays and inhibition. In Methods in enzymology, 514, 205-28. doi:10.1016/B978-0-12-381272-8.00013-1. https://pubmed.ncbi.nlm.nih.gov/22975055/

8. Abizaid, Alfonso, Hougland, James L. 2019. Ghrelin Signaling: GOAT and GHS-R1a Take a LEAP in Complexity. In Trends in endocrinology and metabolism: TEM, 31, 107-117. doi:10.1016/j.tem.2019.09.006. https://pubmed.ncbi.nlm.nih.gov/31636018/

9. Delhanty, P J D, van der Lely, A J. 2011. Ghrelin and glucose homeostasis. In Peptides, 32, 2309-18. doi:10.1016/j.peptides.2011.03.001. https://pubmed.ncbi.nlm.nih.gov/21396419/