Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin

Jithu Varghese James; Joe Varghese; Nikhitha Mariya John; Jean Christophe Deschemin; Sophie Vaulont; Andrew Tristan McKie; Molly Jacob

doi:10.1016/j.jnutbio.2022.109175

Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin

Jithu Varghese James, Joe Varghese, Nikhitha Mariya John, Jean Christophe Deschemin, Sophie Vaulont, Andrew Tristan McKie, Molly Jacob^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations is unclear. To attempt to investigate this, we studied the development of IR and associated inflammation in adipose tissue in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1^−/−) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in various tissues, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1^−/− mice gained less body weight and developed less systemic IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype and indirect evidence of a possible lowered intracellular iron content. The absence of hepcidin was thus associated with attenuated inflammation in the adipose tissue and increased whole-body insulin sensitivity, suggesting a role for it in these processes.

Original language	English
Article number	109175
Journal	JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume	111
DOIs	https://doi.org/10.1016/j.jnutbio.2022.109175
Publication status	Published - Jan 2023

Keywords

Adipose tissue
Hepcidin
Inflammation
Insulin resistance
Iron
Macrophage

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jnutbio.2022.109175

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@article{a5a910827164461eba2806b8c0a98d2d,

title = "Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin",

abstract = "Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations is unclear. To attempt to investigate this, we studied the development of IR and associated inflammation in adipose tissue in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1−/−) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in various tissues, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1−/− mice gained less body weight and developed less systemic IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype and indirect evidence of a possible lowered intracellular iron content. The absence of hepcidin was thus associated with attenuated inflammation in the adipose tissue and increased whole-body insulin sensitivity, suggesting a role for it in these processes.",

keywords = "Adipose tissue, Hepcidin, Inflammation, Insulin resistance, Iron, Macrophage",

author = "James, {Jithu Varghese} and Joe Varghese and John, {Nikhitha Mariya} and Deschemin, {Jean Christophe} and Sophie Vaulont and McKie, {Andrew Tristan} and Molly Jacob",

note = "Funding Information: Research grants awarded to MJ by the Science and Engineering Research Board (SERB) , Government of India ( EMR/2015/000502 ) and a fluid research grant from Christian Medical College , Vellore (IRB no. 8795 , 19th March 2014). JVJ was supported by the SERB grant and then by a Senior Research Fellowship (SRF) from the Indian Council of Medical Research (ICMR), India. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2023",

month = jan,

doi = "10.1016/j.jnutbio.2022.109175",

language = "English",

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T1 - Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin

AU - James, Jithu Varghese

AU - Varghese, Joe

AU - John, Nikhitha Mariya

AU - Deschemin, Jean Christophe

AU - Vaulont, Sophie

AU - McKie, Andrew Tristan

AU - Jacob, Molly

N1 - Funding Information: Research grants awarded to MJ by the Science and Engineering Research Board (SERB) , Government of India ( EMR/2015/000502 ) and a fluid research grant from Christian Medical College , Vellore (IRB no. 8795 , 19th March 2014). JVJ was supported by the SERB grant and then by a Senior Research Fellowship (SRF) from the Indian Council of Medical Research (ICMR), India. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2023/1

Y1 - 2023/1

N2 - Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations is unclear. To attempt to investigate this, we studied the development of IR and associated inflammation in adipose tissue in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1−/−) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in various tissues, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1−/− mice gained less body weight and developed less systemic IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype and indirect evidence of a possible lowered intracellular iron content. The absence of hepcidin was thus associated with attenuated inflammation in the adipose tissue and increased whole-body insulin sensitivity, suggesting a role for it in these processes.

AB - Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations is unclear. To attempt to investigate this, we studied the development of IR and associated inflammation in adipose tissue in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1−/−) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in various tissues, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1−/− mice gained less body weight and developed less systemic IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype and indirect evidence of a possible lowered intracellular iron content. The absence of hepcidin was thus associated with attenuated inflammation in the adipose tissue and increased whole-body insulin sensitivity, suggesting a role for it in these processes.

KW - Adipose tissue

KW - Hepcidin

KW - Inflammation

KW - Insulin resistance

KW - Iron

KW - Macrophage

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AN - SCOPUS:85141345556

SN - 0955-2863

VL - 111

JO - JOURNAL OF NUTRITIONAL BIOCHEMISTRY

JF - JOURNAL OF NUTRITIONAL BIOCHEMISTRY

M1 - 109175

ER -

Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin

Abstract

Keywords

UN SDGs

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