Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice

D. S. Kyung, H. R. Sung, Y. J. Kim, K. D. Kim, S. Y. Cho, J. H. Choi, Y. H. Lee, I. Y. Kim, J. K. Seong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective:Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain.Design:We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses.Results:In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-Associated molecular patterns.Conclusions:Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-Associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

Original languageEnglish
Pages (from-to)755-764
Number of pages10
JournalInternational Journal of Obesity
Volume42
Issue number4
DOIs
Publication statusPublished - 2018 Apr 1

Fingerprint

White Adipose Tissue
Gene Expression Profiling
Adaptive Immunity
Weights and Measures
Weight Loss
Weight Gain
Adipocytes
Adipose Tissue
Up-Regulation
Genes
Diet
Phenotype
Immunophenotyping
Antigen Presentation
T-Lymphocyte Subsets
Body Composition
Major Histocompatibility Complex
Transcriptome
Flow Cytometry
Leukocytes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Kyung, D. S. ; Sung, H. R. ; Kim, Y. J. ; Kim, K. D. ; Cho, S. Y. ; Choi, J. H. ; Lee, Y. H. ; Kim, I. Y. ; Seong, J. K. / Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice. In: International Journal of Obesity. 2018 ; Vol. 42, No. 4. pp. 755-764.
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abstract = "Objective:Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain.Design:We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses.Results:In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-Associated molecular patterns.Conclusions:Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-Associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.",
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Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice. / Kyung, D. S.; Sung, H. R.; Kim, Y. J.; Kim, K. D.; Cho, S. Y.; Choi, J. H.; Lee, Y. H.; Kim, I. Y.; Seong, J. K.

In: International Journal of Obesity, Vol. 42, No. 4, 01.04.2018, p. 755-764.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice

AU - Kyung, D. S.

AU - Sung, H. R.

AU - Kim, Y. J.

AU - Kim, K. D.

AU - Cho, S. Y.

AU - Choi, J. H.

AU - Lee, Y. H.

AU - Kim, I. Y.

AU - Seong, J. K.

PY - 2018/4/1

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N2 - Objective:Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain.Design:We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses.Results:In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-Associated molecular patterns.Conclusions:Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-Associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

AB - Objective:Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain.Design:We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses.Results:In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-Associated molecular patterns.Conclusions:Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-Associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

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