Bmal1 deficiency in neutrophils alleviates symptoms induced by high-fat diet

Brinja Leinweber; Violetta Pilorz; Iwona Olejniczak; Ludmila Skrum; Kimberly Begemann; Isabel Heyde; Sarah Stenger; Christian David Sadik; Henrik Oster

doi:10.1016/j.isci.2025.112038

Bmal1 deficiency in neutrophils alleviates symptoms induced by high-fat diet

Brinja Leinweber, Violetta Pilorz^*, Iwona Olejniczak, Ludmila Skrum, Kimberly Begemann, Isabel Heyde, Sarah Stenger, Christian David Sadik, Henrik Oster^*

^*Korrespondierende/r Autor/-in für diese Arbeit

2 Zitate (Scopus)

Abstract

Physiological processes, including metabolism and immune responses, are generated by the circadian clock, driven by clock genes. Disrupting circadian rhythms through a high-fat diet promotes obesity and inflammation. Studies show that deleting the clock gene, brain, and muscle ARNT-like 1 (Bmal1) in adipose tissue leads to overeating and weight gain. We now show that Bmal1 deletion in neutrophils protects against diet-induced obesity and reduces inflammatory macrophage infiltration into epididymal white adipose tissue (eWAT), despite increased food intake over 20 weeks of a high-fat diet. This protection is linked to enhanced energy expenditure, increased UCP1 expression in iBAT, improved insulin sensitivity, and altered expression of genes encoding chemokine receptors CXCR2, CXCR4, and the ligand Cxcl2 in eWAT. Our findings reveal a key role of Bmal1 in neutrophils in regulating high-fat diet-induced adipose inflammation and emphasize circadian regulation's importance in immuno-metabolic function.

Originalsprache	Englisch
Aufsatznummer	112038
Zeitschrift	iScience
Jahrgang	28
Ausgabenummer	3
ISSN	2589-0042
DOIs	https://doi.org/10.1016/j.isci.2025.112038
Publikationsstatus	Veröffentlicht - 21.03.2025

Fördermittel

This work was supported by a grant from the German Research Foundation, German (OS353-10/1) to HO. We thank our animal caretakers, Sven Schroeder and Kerstin Lünsmann, for their excellent support. We are also grateful to Drs. Geisler and Vollbrandt from the Cell Analysis Core Facility at the University of Lübeck for their invaluable assistance with the use of their equipment. We thank Dr. M. Hirose from the University of Lübeck for reading our article and providing IL-6 and IL-10 primers as a gift. This work was supported by a grant from the German Research Foundation ( OS353-10/1 ) to HO. We thank our animal caretakers, Sven Schroeder and Kerstin Lünsmann, for their excellent support. We are also grateful to Drs. Geisler and Vollbrandt from the Cell Analysis Core Facility at the University of Lübeck for their invaluable assistance with the use of their equipment. We thank Dr. M. Hirose from the University of Lübeck for reading our article and providing IL-6 and IL-10 primers as a gift.

Träger	Trägernummer
Deutsche Forschungsgemeinschaft	OS353-10/1

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 10 – Weniger Ungleichheiten

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

DFG-Fachsystematik

2.22-17 Endokrinologie, Diabetologie, Metabolismus

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10.1016/j.isci.2025.112038

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title = "Bmal1 deficiency in neutrophils alleviates symptoms induced by high-fat diet",

abstract = "Physiological processes, including metabolism and immune responses, are generated by the circadian clock, driven by clock genes. Disrupting circadian rhythms through a high-fat diet promotes obesity and inflammation. Studies show that deleting the clock gene, brain, and muscle ARNT-like 1 (Bmal1) in adipose tissue leads to overeating and weight gain. We now show that Bmal1 deletion in neutrophils protects against diet-induced obesity and reduces inflammatory macrophage infiltration into epididymal white adipose tissue (eWAT), despite increased food intake over 20 weeks of a high-fat diet. This protection is linked to enhanced energy expenditure, increased UCP1 expression in iBAT, improved insulin sensitivity, and altered expression of genes encoding chemokine receptors CXCR2, CXCR4, and the ligand Cxcl2 in eWAT. Our findings reveal a key role of Bmal1 in neutrophils in regulating high-fat diet-induced adipose inflammation and emphasize circadian regulation's importance in immuno-metabolic function.",

author = "Brinja Leinweber and Violetta Pilorz and Iwona Olejniczak and Ludmila Skrum and Kimberly Begemann and Isabel Heyde and Sarah Stenger and Sadik, \{Christian David\} and Henrik Oster",

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AU - Leinweber, Brinja

AU - Pilorz, Violetta

AU - Olejniczak, Iwona

AU - Skrum, Ludmila

AU - Begemann, Kimberly

AU - Heyde, Isabel

AU - Stenger, Sarah

AU - Sadik, Christian David

AU - Oster, Henrik

PY - 2025/3/21

Y1 - 2025/3/21

N2 - Physiological processes, including metabolism and immune responses, are generated by the circadian clock, driven by clock genes. Disrupting circadian rhythms through a high-fat diet promotes obesity and inflammation. Studies show that deleting the clock gene, brain, and muscle ARNT-like 1 (Bmal1) in adipose tissue leads to overeating and weight gain. We now show that Bmal1 deletion in neutrophils protects against diet-induced obesity and reduces inflammatory macrophage infiltration into epididymal white adipose tissue (eWAT), despite increased food intake over 20 weeks of a high-fat diet. This protection is linked to enhanced energy expenditure, increased UCP1 expression in iBAT, improved insulin sensitivity, and altered expression of genes encoding chemokine receptors CXCR2, CXCR4, and the ligand Cxcl2 in eWAT. Our findings reveal a key role of Bmal1 in neutrophils in regulating high-fat diet-induced adipose inflammation and emphasize circadian regulation's importance in immuno-metabolic function.

AB - Physiological processes, including metabolism and immune responses, are generated by the circadian clock, driven by clock genes. Disrupting circadian rhythms through a high-fat diet promotes obesity and inflammation. Studies show that deleting the clock gene, brain, and muscle ARNT-like 1 (Bmal1) in adipose tissue leads to overeating and weight gain. We now show that Bmal1 deletion in neutrophils protects against diet-induced obesity and reduces inflammatory macrophage infiltration into epididymal white adipose tissue (eWAT), despite increased food intake over 20 weeks of a high-fat diet. This protection is linked to enhanced energy expenditure, increased UCP1 expression in iBAT, improved insulin sensitivity, and altered expression of genes encoding chemokine receptors CXCR2, CXCR4, and the ligand Cxcl2 in eWAT. Our findings reveal a key role of Bmal1 in neutrophils in regulating high-fat diet-induced adipose inflammation and emphasize circadian regulation's importance in immuno-metabolic function.

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JO - iScience

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Bmal1 deficiency in neutrophils alleviates symptoms induced by high-fat diet

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

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