Further evidence supporting a potential role for ADH1B in obesity

Liza D. Morales; Douglas T. Cromack; Devjit Tripathy; Marcel Fourcaudot; Satish Kumar; Joanne E. Curran; Melanie Carless; Harald H.H. Göring; Shirley L. Hu; Juan Carlos Lopez-Alvarenga; Kristina M. Garske; Päivi Pajukanta; Kerrin S. Small; Craig A. Glastonbury; Swapan K. Das; Carl Langefeld; Robert L. Hanson; Wen Chi Hsueh; Luke Norton; Rector Arya; Srinivas Mummidi; John Blangero; Ralph A. DeFronzo; Ravindranath Duggirala; Christopher P. Jenkinson

doi:10.1038/s41598-020-80563-z

Further evidence supporting a potential role for ADH1B in obesity

Liza D. Morales, Douglas T. Cromack, Devjit Tripathy, Marcel Fourcaudot, Satish Kumar, Joanne E. Curran, Melanie Carless, Harald H.H. Göring, Shirley L. Hu, Juan Carlos Lopez-Alvarenga, Kristina M. Garske, Päivi Pajukanta, Kerrin S. Small, Craig A. Glastonbury, Swapan K. Das, Carl Langefeld, Robert L. Hanson, Wen Chi Hsueh, Luke Norton, Rector AryaSrinivas Mummidi, John Blangero, Ralph A. DeFronzo, Ravindranath Duggirala, Christopher P. Jenkinson

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Abstract

Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m⁻²) or obese (BMI ≥ 30 kg m⁻²) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.

Original language	English (US)
Article number	1932
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-80563-z
State	Published - Dec 2021

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Morales, L. D., Cromack, D. T., Tripathy, D., Fourcaudot, M., Kumar, S., Curran, J. E., Carless, M., Göring, H. H. H., Hu, S. L., Lopez-Alvarenga, J. C., Garske, K. M., Pajukanta, P., Small, K. S., Glastonbury, C. A., Das, S. K., Langefeld, C., Hanson, R. L., Hsueh, W. C., Norton, L., ... Jenkinson, C. P. (2021). Further evidence supporting a potential role for ADH1B in obesity. Scientific reports, 11(1), Article 1932. https://doi.org/10.1038/s41598-020-80563-z

Morales, LD, Cromack, DT , Tripathy, D, Fourcaudot, M, Kumar, S, Curran, JE, Carless, M, Göring, HHH, Hu, SL, Lopez-Alvarenga, JC, Garske, KM, Pajukanta, P, Small, KS, Glastonbury, CA, Das, SK, Langefeld, C, Hanson, RL, Hsueh, WC, Norton, L, Arya, R, Mummidi, S, Blangero, J, DeFronzo, RA, Duggirala, R & Jenkinson, CP 2021, 'Further evidence supporting a potential role for ADH1B in obesity', Scientific reports, vol. 11, no. 1, 1932. https://doi.org/10.1038/s41598-020-80563-z

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title = "Further evidence supporting a potential role for ADH1B in obesity",

abstract = "Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.",

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AU - Morales, Liza D.

AU - Cromack, Douglas T.

AU - Tripathy, Devjit

AU - Fourcaudot, Marcel

AU - Kumar, Satish

AU - Curran, Joanne E.

AU - Carless, Melanie

AU - Göring, Harald H.H.

AU - Hu, Shirley L.

AU - Lopez-Alvarenga, Juan Carlos

AU - Garske, Kristina M.

AU - Pajukanta, Päivi

AU - Small, Kerrin S.

AU - Glastonbury, Craig A.

AU - Das, Swapan K.

AU - Langefeld, Carl

AU - Hanson, Robert L.

AU - Hsueh, Wen Chi

AU - Norton, Luke

AU - Arya, Rector

AU - Mummidi, Srinivas

AU - Blangero, John

AU - DeFronzo, Ralph A.

AU - Duggirala, Ravindranath

AU - Jenkinson, Christopher P.

PY - 2021/12

Y1 - 2021/12

N2 - Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.

AB - Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.

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Further evidence supporting a potential role for ADH1B in obesity

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