scholarly journals Myeloid-specific deletion of Zfp36 protects against insulin resistance and fatty liver in diet-induced obese mice

2018 ◽  
Vol 315 (4) ◽  
pp. E676-E693 ◽  
Author(s):  
Valentina Caracciolo ◽  
Jeanette Young ◽  
Donna Gonzales ◽  
Yingchun Ni ◽  
Stephen J. Flowers ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Mrna Expression ◽  
Zinc Finger Protein ◽  
Inflammatory Responses ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation ◽  
Mrna Binding

Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc finger protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild-type (Control) mice became obese and diabetic on a high-fat diet, and obese mice with myeloid-specific loss of Zfp36 [knockout (KO)] demonstrated increased adipose tissue and liver cytokine mRNA expression compared with Control mice. Unexpectedly, in glucose tolerance testing and hyperinsulinemic-euglycemic clamp studies, myeloid Zfp36 KO mice demonstrated improved insulin sensitivity compared with Control mice. Obese KO and Control mice had similar macrophage infiltration of the adipose depots and similar peripheral cytokine levels, but lean and obese KO mice demonstrated increased Kupffer cell (KC; the hepatic macrophage)-expressed Mac2 compared with lean Control mice. Insulin resistance in obese Control mice was associated with enhanced Zfp36 expression in KCs. Compared with Control mice, KO mice demonstrated increased hepatic mRNA expression of a multitude of classical (M1) inflammatory cytokines/chemokines, and this M1-inflammatory hepatic milieu was associated with enhanced nuclear localization of IKKβ and the p65 subunit of NF-κB. Our data confirm the important role of innate immune cells in regulating hepatic insulin sensitivity and lipid metabolism, challenge-prevailing models in which M1 inflammatory responses predict insulin resistance, and indicate that myeloid-expressed Zfp36 modulates the response to insulin in mice.

Angiopoietin-like 8 Improves Insulin Resistance and Attenuates Adipose Tissue Inflammation in Diet-Induced Obese Mice

2018 ◽  
Vol 128 (05) ◽  
pp. 290-296 ◽  
Author(s):  
Deng Luo ◽  
Xiaolin Chen ◽  
Wenqiang Yang ◽  
Wenzhuo Ran ◽  
Zhongyuan Wen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
M2 Macrophage ◽  
Dependent Manner ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation ◽  
M1 Macrophage ◽  
Dose Dependent

AbstractAngiopoietin-like 8 (ANGPTL8) is closely linked to obesity-associated metabolic diseases and insulin resistance. The aim of the current study was to investigate the ability of ANGPTL8 to reverse insulin resistance in obese mice. The administration of ANGPTL8 reduced weight gain and improved glucose tolerance in mice with diet-induced obesity. In addition, ANGPTL8 administration modified macrophage infiltration, reduced monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β(IL-1β) levels, and increased adiponectin gene expression in inguinal white adipose tissue (iWAT). Moreover, the exposure of a cultured peritoneal macrophage line to ANGPTL8 reduced the mRNA expression of M1 macrophage markers (TNF-α and IL-1β) upon stimulation with lipopolysaccharides in a dose-dependent manner. By contrast, when incubated with IL-4, exposure of macrophages to ANGPTL8 increased the mRNA expression of M2 macrophage markers (Arg1 and Chi3l3) in a dose-dependent manner. Collectively, the results of the present study demonstrated that treatment with ANGPTL8 can attenuate adipose tissue inflammation through regulation of macrophage polarization, and thus, it could be useful for improving insulin resistance.

scholarly journals Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice

2008 ◽  
Vol 295 (3) ◽  
pp. E586-E594 ◽  
Author(s):  
Richard L. Bradley ◽  
Justin Y. Jeon ◽  
Fen-Fen Liu ◽  
Eleftheria Maratos-Flier
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Voluntary Exercise ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation

Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high sucrose diet (HFD). Over four wk, mice fed chow gained 2.3 ± 0.3 g, while HFD mice gained 6.8 ± 0.5 g. After 4 wk, mice were subdivided into four groups: chow-no exercise, chow-exercise, HFD-no exercise, HFD-exercise and monitored for an additional 6 wk. Chow-no exercise and HFD-no exercise mice gained an additional 1.2 ± 0.3 g and 3.3 ± 0.5 g respectively. Exercising mice had higher food consumption, but did not gain additional weight. As expected, GTT and ITT showed impaired glucose tolerance and insulin resistance in HFD-no exercise mice. However, glucose tolerance improved significantly and insulin sensitivity was completely normalized in HFD-exercise animals. Furthermore, expression of TNF-α, MCP-1, PAI-1 and IKKβ was increased in adipose tissue from HFD mice compared with chow mice, whereas exercise reversed the increased expression of these inflammatory cytokines. In contrast, expression of these cytokines in liver was unchanged among the four groups. These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD.

Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet‐induced obese mice

2017 ◽  
Vol 31 (5) ◽  
pp. 2135-2145 ◽  
Author(s):  
Leyre Martínez-Fernández ◽  
Pedro González-Muniesa ◽  
Laura M. Laiglesia ◽  
Neira Sáinz ◽  
Pedro L. Prieto-Hontoria ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation ◽  
Maresin 1

Self-Assembled Hyaluronic Acid Nanoparticles Ameliorate Adipose Tissue Inflammation and Insulin Resistance in Diet-Induced Obese Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2003-P ◽  
Author(s):  
JUN GI RHO ◽  
WANGHEE LEE ◽  
EUNYOUNG LEE ◽  
CHONGTAE KIM ◽  
EUN KYUNG LEE ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hyaluronic Acid ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation ◽  
Self Assembled

Increased GIP signaling induces adipose inflammation via a HIF-1α-dependent pathway and impairs insulin sensitivity in mice

2015 ◽  
Vol 308 (5) ◽  
pp. E414-E425 ◽  
Author(s):  
Shu Chen ◽  
Fumiaki Okahara ◽  
Noriko Osaki ◽  
Akira Shimotoyodome
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Inflammation ◽  
Obesity And Diabetes ◽  
Gut Hormone

Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone secreted in response to dietary fat and glucose. The blood GIP level is elevated in obesity and diabetes. GIP stimulates proinflammatory gene expression and impairs insulin sensitivity in cultured adipocytes. In obesity, hypoxia within adipose tissue can induce inflammation. The aims of this study were 1) to examine the proinflammatory effect of increased GIP signaling in adipose tissues in vivo and 2) to clarify the association between GIP and hypoxic signaling in adipose tissue inflammation. We administered GIP intraperitoneally to misty (lean) and db/db (obese) mice and examined adipose tissue inflammation and insulin sensitivity. We also examined the effects of GIP and hypoxia on expression of the GIP receptor (GIPR) gene and proinflammatory genes in 3T3-L1 adipocytes. GIP administration increased monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration into adipose tissue and increased blood glucose in db/db mice. GIPR and hypoxia-inducible factor-1α (HIF-1α) expressions were positively correlated in the adipose tissue in mice. GIPR expression increased dramatically in differentiated adipocytes. GIP treatment of adipocytes increased MCP-1 and interleukin-6 (IL-6) production. Adipocytes cultured either with RAW 264 macrophages or under hypoxia expressed more GIPR and HIF-1α, and GIP treatment increased gene expression of plasminogen activator inhibitor 1 and IL-6. HIF-1α gene silencing diminished both macrophage- and hypoxia-induced GIPR expression and GIP-induced IL-6 expression in adipocytes. Thus, increased GIP signaling plays a significant role in adipose tissue inflammation and thereby insulin resistance in obese mice, and HIF-1α may contribute to this process.

scholarly journals Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice

2009 ◽  
Vol 296 (5) ◽  
pp. E1164-E1171 ◽  
Author(s):  
Victoria J. Vieira ◽  
Rudy J. Valentine ◽  
Kenneth R. Wilund ◽  
Nirav Antao ◽  
Tracy Baynard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Metabolic Disturbances ◽  
Low Fat ◽  
Tissue Inflammation ◽  
Low Fat Diet ◽  
Tnf Α

Adipose tissue inflammation causes metabolic disturbances, including insulin resistance and hepatic steatosis. Exercise training (EX) may decrease adipose tissue inflammation, thereby ameliorating such disturbances, even in the absence of fat loss. The purpose of this study was to 1) compare the effects of low-fat diet (LFD), EX, and their combination on inflammation, insulin resistance, and hepatic steatosis in high-fat diet-induced obese mice and 2) determine the effect of intervention duration (i.e., 6 vs. 12 wk). C57BL/6 mice ( n = 109) fed a 45% fat diet (HFD) for 6 wk were randomly assigned to an EX (treadmill: 5 days/wk, 6 or 12 wk, 40 min/day, 65–70% V̇o2max) or sedentary (SED) group. Mice remained on HFD or were placed on a 10% fat diet (LFD) for 6 or 12 wk. Following interventions, fat pads were weighed and expressed relative to body weight; hepatic steatosis was assessed by total liver triglyceride and insulin resistance by HOMA-IR and glucose AUC. RT-PCR was used to determine adipose gene expression of MCP-1, F4/80, TNF-α, and leptin. By 12 wk, MCP-1, F4/80, and TNF-α mRNA were reduced by EX and LFD. Exercise ( P = 0.02), adiposity ( P = 0.03), and adipose F4/80 ( P = 0.02) predicted reductions in HOMA-IR ( r2 = 0.75, P < 0.001); only adiposity ( P = 0.04) predicted improvements in hepatic steatosis ( r2 = 0.51, P < 0.001). Compared with LFD, EX attenuated increases in adiposity, hepatic steatosis, and adipose MCP-1 expression from 6 to 12 wk. There are unique metabolic consequences of a sedentary lifestyle and HFD that are most evident long term, highlighting the importance of both EX and LFD in preventing obesity-related metabolic disturbances.

scholarly journals Enzamin improves adipose tissue inflammation with impaired adipocytokine expression and insulin resistance in obese mice (688.1)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Osamu Matsuo ◽  
Yukinori Tamura ◽  
Masato Yano ◽  
Naoyuki Kawao ◽  
Shigeru Ueshima ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation
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