Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain

Abstract

IntroductionEnlarged adipose tissue is characterized by infiltration of activated immune cells and increased expression of chemokines recruiting these cells including C-C motif ligand 19 (CCL19), although the role of adipose CCL19 is still inconclusive.Research design and methodsAdipocyte-specific Ccl19 knock-in (KI) mice were generated, and the mice were fed either a normal diet or 40% or 60% fat diet (FD) to investigate the effects of CCL19 on the induction of inflammation and lipid metabolism.ResultsCcl19KI mice exhibited increased inflammatory signs in adipose tissue and enlarged subcutaneous white and brown adipose tissue than those of wild-type (WT) mice. The adipose tissue of Ccl19KI mice was characterized by increased extracellular signal-regulated kinase 1/2 and decreased AMP-activated protein kinase α phosphorylation. The protein expression of peroxisome proliferator-activated receptor γ coactivator 1α and uncoupling protein 1 was significantly reduced in brown adipose tissue of Ccl19KI mice compared with that in WT mice. The most remarkable changes between genotypes were observed in mice fed a 40% FD.ConclusionA 40% FD enhanced the effects of CCL19 overexpression, and these mice could be a suitable model to study metabolic disorders in overweight Asians.

The bidirectional association between diabetes and periodontitis, from basic to clinical

“…CCR7 deficient mice were prevented from HFD-induced gain of body weight and metabolic abnormalities in adipose tissue [22] , [72] . In contrast, adipocyte-specific CCL19 overexpression enhanced western-diet-induced body weight gain and insulin resistance by upregulation of inflammation in visceral adipose tissue [73] . Taken together, DC infiltration via the CCL19-CCR7 axis, resulting from amplified microinflammation derived from adipocyte-macrophage interactions, might be an essential factor in the maturation and induction of microinflammation in adipose tissue ( Fig.…”

Integrative Analysis of Metabolomic and Transcriptomic Data Reveals the Antioxidant Potential of Dietary Lutein in Chickens

“…For example, the expression of the CCL19 gene was significantly reduced in the lutein group. Compared with wild-type mice, CCL19 knock-in mice showed increased inflammation in adipose tissue and increased subcutaneous white and brown adipose tissue ( 34 ). The expression of the CCL19 gene is increased in obese human adipose tissue and is positively correlated with markers of insulin resistance and metabolism, indicating that CCL19 may be an essential marker for predicting insulin resistance and metabolism ( 35 ).…”

XAF1 overexpression exacerbates diabetes by promoting pancreatic β-cell apoptosis

“…1a). Diets fed the mice were the same as those used in the previous report [ 14 ], as described in the supplementary information. The animal study was reviewed and approved by Institutional Animal Care and Use Committee of the University of Kyushu (protocol #A20-101–0 and #1–7).…”

“…Immunofluorescence staining was performed as described previously [ 14 ] using the antibodies listed in the supplementary information. Paraffin-embedded tissues of mice samples were cut into 5 µm sections and they were dewaxed in xylene and rehydrated in graded ethanol solutions.…”