Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

Pernille Barkholt; Kristoffer T. G. Rigbolt; Mechthilde Falkenhahn; Thomas Huebschle; Uwe Schwahn; Maria Luisa Fernandez-Cachon; Thorsten Schmidt; Stefan Theis; Henrik H. Hansen; Anders Hay-Schmidt; Philip J. Pedersen; Niels Vrang; Jacob Jelsing

doi:10.1038/s41598-019-52257-8

Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

Pernille Barkholt, Kristoffer T. G. Rigbolt, Mechthilde Falkenhahn, Thomas Huebschle, Uwe Schwahn, Maria Luisa Fernandez-Cachon, Thorsten Schmidt, Stefan Theis, Henrik H. Hansen, Anders Hay-Schmidt, Philip J. Pedersen, Niels Vrang, Jacob Jelsing

Section 01 - Prosthetics

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Abstract

The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

Original language	English
Article number	16161
Journal	Scientific Reports
Volume	9
Number of pages	10
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-019-52257-8
Publication status	Published - 1 Dec 2019

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Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight lossFinal published version, 2.09 MBLicence: CC BY

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Barkholt, P., Rigbolt, K. T. G., Falkenhahn, M., Huebschle, T., Schwahn, U., Fernandez-Cachon, M. L., Schmidt, T., Theis, S., Hansen, H. H., Hay-Schmidt, A., Pedersen, P. J., Vrang, N., & Jelsing, J. (2019). Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss. Scientific Reports, 9, [16161 ]. https://doi.org/10.1038/s41598-019-52257-8

Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss. / Barkholt, Pernille; Rigbolt, Kristoffer T. G.; Falkenhahn, Mechthilde et al.

In: Scientific Reports, Vol. 9, 16161 , 01.12.2019.

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

Barkholt, P, Rigbolt, KTG, Falkenhahn, M, Huebschle, T, Schwahn, U, Fernandez-Cachon, ML, Schmidt, T, Theis, S, Hansen, HH, Hay-Schmidt, A, Pedersen, PJ, Vrang, N & Jelsing, J 2019, 'Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss', Scientific Reports, vol. 9, 16161 . https://doi.org/10.1038/s41598-019-52257-8

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title = "Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss",

abstract = "The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.",

author = "Pernille Barkholt and Rigbolt, {Kristoffer T. G.} and Mechthilde Falkenhahn and Thomas Huebschle and Uwe Schwahn and Fernandez-Cachon, {Maria Luisa} and Thorsten Schmidt and Stefan Theis and Hansen, {Henrik H.} and Anders Hay-Schmidt and Pedersen, {Philip J.} and Niels Vrang and Jacob Jelsing",

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doi = "10.1038/s41598-019-52257-8",

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T1 - Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

AU - Barkholt, Pernille

AU - Rigbolt, Kristoffer T. G.

AU - Falkenhahn, Mechthilde

AU - Huebschle, Thomas

AU - Schwahn, Uwe

AU - Fernandez-Cachon, Maria Luisa

AU - Schmidt, Thorsten

AU - Theis, Stefan

AU - Hansen, Henrik H.

AU - Hay-Schmidt, Anders

AU - Pedersen, Philip J.

AU - Vrang, Niels

AU - Jelsing, Jacob

PY - 2019/12/1

Y1 - 2019/12/1

N2 - The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

AB - The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

U2 - 10.1038/s41598-019-52257-8

DO - 10.1038/s41598-019-52257-8

M3 - Journal article

C2 - 31695063

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 16161

ER -

Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

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