BIOMAT Database Logo BIOMAT Database Logo

CX3CL1-CX3CR1 Signaling Deficiency Exacerbates Obesity-induced Inflammation and Insulin Resistance in Male Mice. 2021

Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
Advanced Preventive Medical Sciences Research Center, Kanazawa University, Kanazawa, Japan.

The CX3CL1-CX3CR1 system plays an important role in disease progression by regulating inflammation both positively and negatively. We reported previously that C-C chemokine receptors 2 and 5 promote obesity-associated adipose tissue inflammation and insulin resistance. Here, we demonstrate that CX3CL1-CX3CR1 signaling is involved in adipose tissue inflammation and insulin resistance in obese mice via adipose tissue macrophage recruitment and M1/M2 polarization. Cx3cl1 expression was persistently decreased in the epididymal white adipose tissue (eWAT) of high-fat diet-induced obese (DIO) mice, despite increased expression of other chemokines. Interestingly, in Cx3cr1-/- mice, glucose tolerance, insulin resistance, and hepatic steatosis induced by DIO or leptin deficiency were exacerbated. CX3CL1-CX3CR1 signaling deficiency resulted in reduced M2-polarized macrophage migration and an M1-dominant shift of macrophages within eWAT. Furthermore, transplantation of Cx3cr1-/- bone marrow was sufficient to impair glucose tolerance, insulin sensitivity, and regulation of M1/M2 status. Moreover, Cx3cl1 administration in vivo led to the attenuation of glucose intolerance and insulin resistance. Thus, therapy targeting the CX3CL1-CX3CR1 system may be beneficial in the treatment of type 2 diabetes by regulating M1/M2 macrophages.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008820 Mice, Obese Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid. Hyperglycemic Mice,Obese Mice,Mouse, Hyperglycemic,Mouse, Obese,Hyperglycemic Mouse,Mice, Hyperglycemic,Obese Mouse
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000073883 CX3C Chemokine Receptor 1 Receptor for CHEMOKINE CX3CL1 expressed by lymphocytes, neurons, and GLIAL CELLS. Its interaction with CX3CL1 mediates CELL ADHESION and CELL MIGRATION. It also functions as a co-receptor with the CD4 ANTIGEN for HIV-1 in vitro. CX(3)C Receptor,CX(3)CR1,CX3C Receptor,Fractalkine Receptor,Receptor, V28,V28 Receptor,V28 Receptors,Receptor, CX3C,Receptor, Fractalkine,Receptors, V28
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

Related Publications

Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
CARD3 deficiency exacerbates diet-induced obesity, hepatosteatosis, and insulin resistance in male mice.
February 2013, Endocrinology,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance.
May 2013, American journal of physiology. Endocrinology and metabolism,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice.
June 2014, Endocrinology,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
CX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver inflammation and fibrosis in mice.
October 2010, Hepatology (Baltimore, Md.),
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
Vinexin β deficiency exacerbates diet-induced obesity, hepatosteatosis, insulin resistance and endoplasmic reticulum stress in mice.
March 2022, Biochemical and biophysical research communications,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
Myeloid-derived grancalcin instigates obesity-induced insulin resistance and metabolic inflammation in male mice.
January 2024, Nature communications,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis.
April 2024, International journal of molecular sciences,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity.
May 2014, American journal of physiology. Endocrinology and metabolism,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
PARP1 deficiency exacerbates diet-induced obesity in mice.
June 2010, The Journal of endocrinology,
Mayumi Nagashimada, and Kazuki Sawamoto, and Yinhua Ni, and Hironori Kitade, and Naoto Nagata, and Liang Xu, and Masuko Kobori, and Naofumi Mukaida, and Tatsuya Yamashita, and Shuichi Kaneko, and Tsuguhito Ota
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling.
January 2014, Frontiers in cellular neuroscience,
Copied contents to your clipboard!