Transcriptional Regulation of Metabolism in the Intestinal Epithelium

Overview

Journal Am J Physiol Gastrointest Liver Physiol

Publisher American Physiological Society

Specialties Gastroenterology
Physiology

Date 2023 Oct 3

PMID 37786942

Authors

Joseph Burclaff

Affiliations

Soon will be listed here.

Abstract

Epithelial metabolism in the intestine is increasingly known to be important for stem cell maintenance and activity while also affecting weight gain and diseases. This review compiles studies from recent years which describe major transcription factors controlling metabolic activity across the intestinal epithelium as well as transcriptional and epigenetic networks controlling the factors themselves. Recent studies show that transcriptional regulators serve as the link between signals from the microbiota and diet and epithelial metabolism. Studies have advanced this paradigm to identify druggable targets to block weight gain or disease progression in mice. As such, there is great potential that a better understanding of these regulatory networks will improve our knowledge of intestinal physiology and promote discoveries to benefit human health.

References

Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M, Gavrilova O . Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med. 2011; 17(12):1585-93. PMC: 3902046. DOI: 10.1038/nm.2505. View

Cunningham K, Vincent G, Sodhi C, Novak E, Ranganathan S, Egan C . Peroxisome Proliferator-activated Receptor-γ Coactivator 1-α (PGC1α) Protects against Experimental Murine Colitis. J Biol Chem. 2016; 291(19):10184-200. PMC: 4858969. DOI: 10.1074/jbc.M115.688812. View

Balakrishnan A . Micromanaging the gut: unravelling the regulatory pathways that mediate the intestinal adaptive response. Ann R Coll Surg Engl. 2018; 100(3):165-171. PMC: 5930084. DOI: 10.1308/rcsann.2017.0174. View

Bara A, Chen L, Ma C, Underwood J, Moreci R, Sumigray K . Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut. Development. 2022; 149(23). PMC: 10112929. DOI: 10.1242/dev.201251. View

Yu F, Wang Z, Zhang T, Chen X, Xu H, Wang F . Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding. Nat Commun. 2021; 12(1):5323. PMC: 8423749. DOI: 10.1038/s41467-021-25674-5. View

Cheng C, Biton M, Haber A, Gunduz N, Eng G, Gaynor L . Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis and Adaptation to Diet. Cell. 2019; 178(5):1115-1131.e15. PMC: 6732196. DOI: 10.1016/j.cell.2019.07.048. View

Davison J, Lickwar C, Song L, Breton G, Crawford G, Rawls J . Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha. Genome Res. 2017; 27(7):1195-1206. PMC: 5495071. DOI: 10.1101/gr.220111.116. View

Kuang Z, Wang Y, Li Y, Ye C, Ruhn K, Behrendt C . The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science. 2019; 365(6460):1428-1434. PMC: 7158748. DOI: 10.1126/science.aaw3134. View

DErrico I, Salvatore L, Murzilli S, Lo Sasso G, Latorre D, Martelli N . Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1alpha) is a metabolic regulator of intestinal epithelial cell fate. Proc Natl Acad Sci U S A. 2011; 108(16):6603-8. PMC: 3081029. DOI: 10.1073/pnas.1016354108. View

10.

Ludikhuize M, Meerlo M, Gallego M, Xanthakis D, Burgaya Julia M, Nguyen N . Mitochondria Define Intestinal Stem Cell Differentiation Downstream of a FOXO/Notch Axis. Cell Metab. 2020; 32(5):889-900.e7. DOI: 10.1016/j.cmet.2020.10.005. View

11.

Wen J, Mercado G, Volland A, Doden H, Lickwar C, Crooks T . Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine. Sci Adv. 2021; 7(30). PMC: 8302129. DOI: 10.1126/sciadv.abg1371. View

12.

Sussman W, Stevenson M, Mowdawalla C, Mota S, Ragolia L, Pan X . BMAL1 controls glucose uptake through paired-homeodomain transcription factor 4 in differentiated Caco-2 cells. Am J Physiol Cell Physiol. 2019; 317(3):C492-C501. PMC: 6766619. DOI: 10.1152/ajpcell.00058.2019. View

13.

Desvergne B, Michalik L, Wahli W . Transcriptional regulation of metabolism. Physiol Rev. 2006; 86(2):465-514. DOI: 10.1152/physrev.00025.2005. View

14.

Stoffel M, Duncan S . The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci U S A. 1997; 94(24):13209-14. PMC: 24288. DOI: 10.1073/pnas.94.24.13209. View

15.

Cosovanu C, Resch P, Jordan S, Lehmann A, Ralser M, Farztdinov V . Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice. J Exp Med. 2022; 219(12). PMC: 9486084. DOI: 10.1084/jem.20220233. View

16.

Thompson C, DeLaForest A, Battle M . Patterning the gastrointestinal epithelium to confer regional-specific functions. Dev Biol. 2018; 435(2):97-108. PMC: 6615902. DOI: 10.1016/j.ydbio.2018.01.006. View

17.

Burclaff J, Bliton R, Breau K, Ok M, Gomez-Martinez I, Ranek J . A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics. Cell Mol Gastroenterol Hepatol. 2022; 13(5):1554-1589. PMC: 9043569. DOI: 10.1016/j.jcmgh.2022.02.007. View

18.

Diamanti K, Cavalli M, Pereira M, Pan G, Castillejo-Lopez C, Kumar C . Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes, and normal tissues. Cell Rep Med. 2022; 3(10):100763. PMC: 9589007. DOI: 10.1016/j.xcrm.2022.100763. View

19.

Kim J, Li C, Weiss H, Zhou Y, Liu C, Wang Q . Regulation of Ketogenic Enzyme HMGCS2 by Wnt/β-catenin/PPARγ Pathway in Intestinal Cells. Cells. 2019; 8(9). PMC: 6770209. DOI: 10.3390/cells8091106. View

20.

Choi J, Zhang X, Li W, Houston M, Peregrina K, Dubin R . Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis. Mol Cancer Res. 2023; 21(8):808-824. PMC: 10390890. DOI: 10.1158/1541-7786.MCR-22-1000. View