Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function

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Standard

Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function. / Huang, Mi; Prasad, Rashmi B; Coral, Daniel E; Hjort, Line; Minja, Daniel T R; Mulder, Hindrik; Franks, Paul W; Kalamajski, Sebastian.

In: Diabetes, Vol. 73, No. 4, 2024, p. 637-645.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Huang, M, Prasad, RB, Coral, DE, Hjort, L, Minja, DTR, Mulder, H, Franks, PW & Kalamajski, S 2024, 'Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function', Diabetes, vol. 73, no. 4, pp. 637-645. https://doi.org/10.2337/db23-0531

APA

Huang, M., Prasad, R. B., Coral, D. E., Hjort, L., Minja, D. T. R., Mulder, H., Franks, P. W., & Kalamajski, S. (2024). Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function. Diabetes, 73(4), 637-645. https://doi.org/10.2337/db23-0531

Vancouver

Huang M, Prasad RB, Coral DE, Hjort L, Minja DTR, Mulder H et al. Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function. Diabetes. 2024;73(4):637-645. https://doi.org/10.2337/db23-0531

Author

Huang, Mi ; Prasad, Rashmi B ; Coral, Daniel E ; Hjort, Line ; Minja, Daniel T R ; Mulder, Hindrik ; Franks, Paul W ; Kalamajski, Sebastian. / Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function. In: Diabetes. 2024 ; Vol. 73, No. 4. pp. 637-645.

Bibtex

@article{374d70dd9e8a439db7531961fbcfa21d,
title = "Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function",
abstract = "Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used CRISPR/Cas9 to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line (hBAs). Switching the rs10071329 genotype from A/A to G/G enhanced PPARGC1B expression throughout the adipogenic differentiation, identifying rs10071329 as a cis-eQTL. The higher PPARGC1B expression in G/G cells coincided with greater accumulation of triglycerides, and higher expression of mitochondria-encoded genes, but without significant effects on adipogenic marker expression. Furthermore, G/G cells had improved basal- and norepinephrine-stimulated mitochondrial respiration, possibly relating to enhanced mitochondrial gene expression. The G/G cells also exhibited increased norepinephrine-stimulated glycerol release, indicating improved lipolysis. Altogether, our results showed that rs10071329 is a cis-eQTL, with the G/G genotype conferring enhanced PPARGC1B expression, with consequent improved mitochondrial function and response to norepinephrine in brown adipocytes. This genetic variant, and as yet undetermined eQTLs, at PPARGC1B could prove useful in genotype-based precision medicine for obesity treatment.",
author = "Mi Huang and Prasad, {Rashmi B} and Coral, {Daniel E} and Line Hjort and Minja, {Daniel T R} and Hindrik Mulder and Franks, {Paul W} and Sebastian Kalamajski",
note = "{\textcopyright} 2024 by the American Diabetes Association.",
year = "2024",
doi = "10.2337/db23-0531",
language = "English",
volume = "73",
pages = "637--645",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "4",

}

RIS

TY - JOUR

T1 - Human Genetic Variation at rs10071329 Correlates with Adiposity-related Traits, Modulates PPARGC1B Expression, and Alters Brown Adipocyte Function

AU - Huang, Mi

AU - Prasad, Rashmi B

AU - Coral, Daniel E

AU - Hjort, Line

AU - Minja, Daniel T R

AU - Mulder, Hindrik

AU - Franks, Paul W

AU - Kalamajski, Sebastian

N1 - © 2024 by the American Diabetes Association.

PY - 2024

Y1 - 2024

N2 - Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used CRISPR/Cas9 to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line (hBAs). Switching the rs10071329 genotype from A/A to G/G enhanced PPARGC1B expression throughout the adipogenic differentiation, identifying rs10071329 as a cis-eQTL. The higher PPARGC1B expression in G/G cells coincided with greater accumulation of triglycerides, and higher expression of mitochondria-encoded genes, but without significant effects on adipogenic marker expression. Furthermore, G/G cells had improved basal- and norepinephrine-stimulated mitochondrial respiration, possibly relating to enhanced mitochondrial gene expression. The G/G cells also exhibited increased norepinephrine-stimulated glycerol release, indicating improved lipolysis. Altogether, our results showed that rs10071329 is a cis-eQTL, with the G/G genotype conferring enhanced PPARGC1B expression, with consequent improved mitochondrial function and response to norepinephrine in brown adipocytes. This genetic variant, and as yet undetermined eQTLs, at PPARGC1B could prove useful in genotype-based precision medicine for obesity treatment.

AB - Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used CRISPR/Cas9 to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line (hBAs). Switching the rs10071329 genotype from A/A to G/G enhanced PPARGC1B expression throughout the adipogenic differentiation, identifying rs10071329 as a cis-eQTL. The higher PPARGC1B expression in G/G cells coincided with greater accumulation of triglycerides, and higher expression of mitochondria-encoded genes, but without significant effects on adipogenic marker expression. Furthermore, G/G cells had improved basal- and norepinephrine-stimulated mitochondrial respiration, possibly relating to enhanced mitochondrial gene expression. The G/G cells also exhibited increased norepinephrine-stimulated glycerol release, indicating improved lipolysis. Altogether, our results showed that rs10071329 is a cis-eQTL, with the G/G genotype conferring enhanced PPARGC1B expression, with consequent improved mitochondrial function and response to norepinephrine in brown adipocytes. This genetic variant, and as yet undetermined eQTLs, at PPARGC1B could prove useful in genotype-based precision medicine for obesity treatment.

U2 - 10.2337/db23-0531

DO - 10.2337/db23-0531

M3 - Journal article

C2 - 38190589

VL - 73

SP - 637

EP - 645

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -

ID: 379593595