In obesity and weight loss, all roads lead to the mighty macrophage

Eagle, Alex Red; Chawla, Ajay

doi:10.1172/jci44721

Cited by 30 publications

(32 citation statements)

References 20 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adipose tissue macrophages (ATMs) are classified into classical activated macrophages (also known as M1 macrophages) and alternatively activated macrophages (also known as M2 macrophages). It is well known that M1 macrophages infiltration of WAT triggers inflammation, while M2 macrophages suppress inflammation4546. Obviously, purified EPS administration induced the M2 macrophages and inhibited M1 macrophages in adipose tissue and liver, which explained the improved inflammation status by EPS.…”

Section: Discussionmentioning

confidence: 90%

Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice

Zhang

Zhou

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The fibroblast cell line of 3T3-L1 was used as a cell model for screening and evaluating the feasibility of probiotic components in improving animal lipid metabolisms. The extracts from 12 Lactobacillus strains caused significantly reduced triacylglycerol (TAG) accumulation but with severe inflammation induction in 3T3-L1 adipocytes. Interestingly, exopolysaccharides (EPS) from LGG (Lactobacillus rhamnosus GG) significantly decreased the TAG accumulation without any inflammation. The anti-obesity effect of EPS was confirmed in high-fat-diets feeding mice. Fat pads of mice injected with EPS (50 mg/kg) every two days for two weeks were significantly reduced with much smaller adipocytes, compared with the counterparts. The levels of TAG and cholesterol ester in liver, as well as serum TAG, were decreased in EPS injected mice. In addition, down-regulated inflammation was observed in adipose tissue and liver. Interestingly, the expression of TLR2 in adipose tissue and 3T3-L1 cells was significantly increased by EPS addition. Moreover, the reverse of TAG accumulation in TLR2 knockdown 3T3-L1 in the presence of EPS confirmed that the inhibition effect of EPS on adipogenesis was mediated by TLR2. EPS from LGG has the potential for therapeutic development to intervene lipid metabolic disorders in mammals.

show abstract

Section: Discussionmentioning

confidence: 90%

Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice

Zhang

Zhou

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Recent studies suggested that macrophage recruitment to adipose tissue is a normal response that associates with activation of adipocyte lipolysis during the early phase of weight loss and fasting ( 8,23 ). However, the metabolic factors that induce ATM infi ltration during lipolysis are still undefi ned.…”

Section: Discussionmentioning

confidence: 99%

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

Cifarelli

Sun

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

Supplementary key words adipose tissue • cyclooxygenase • eicosanoids • extracellular signal-regulated kinase • fatty acid • infl ammation • lipaseAdipose tissue is the major repository of excess energy stored in the form of triacylglycerol (TAG). During energy need, adipocyte lipolysis involving the hydrolysis of TAG releases FFAs for energy production by different tissues ( 1, 2 ). Adipose tissue also secretes various adipokines, which infl uence energy homeostasis and insulin sensitivity of distant tissues ( 3, 4 ). In addition to its important role in metabolic regulation, adipose tissue modulates the immune system by recruiting and activating lymphoid and myeloid cells when adipocyte fat storage is exaggerated as occurs in obesity ( 5 ). In obese individuals, there is a strong positive correlation between adipocyte size and the accumulation of proinfl ammatory adipose tissue macrophages (ATMs) ( 6, 7 ).However, ATM recruitment also occurs in mice after fasting or with calorie restriction ( 8 ) and in obese patients maintained on low-calorie diets during early weight loss ( 9 ), but under these conditions, it does not associate with infl ammation. The above fi ndings suggest that the mechanisms that operate in ATM recruitment in obesity or calorie restriction are not identical. Both fasting and pharmaceutically induced lipolysis increase macrophage content in adipose tissue, and lipolysis measures correlate with increased ATM content independent of adiposity ( 10 ). This suggests that lipid turnover and not lipid accumulation per se is Abstract Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic infl ammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinfl ammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specifi c lipid mediators with anti-infl ammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E 2 (PGE 2 ) and prostaglandin D 2 (PGD 2 ), refl ecting cytosolic phospholipase A 2 ␣ activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-infl ammatory PGE 2 potently induced macrophage migration while different FFAs and PGD 2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE 2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE 2 with infl ammation suppressive properties plays a signifi cant rol...

show abstract

“…We extend these observations by demonstrating that exogenous administration of TNF-␣ can impair function in eWAT arteries from NC-, but not HF-fed, mice and that the chronic in vivo exposure of eWAT arteries to elevated TNF-␣ resulting from HF feeding underlies the observed endothelial dysfunction. Although the causal role of adipose tissue dysfunction and inflammation in obesity-associated metabolic and cardiovascular disease risk is well established (3,15,24,32), there is surprisingly little information regarding the role of vascular function per se in the overall function/phenotype of the adipose tissue (30), or how this vascular function is affected by obesity (12). Here, we provide direct evidence for a HF-diet-mediated, TNF-␣-induced, impairment in adipose tissue arterial function that may have important implications for tissue-specific and systemic metabolic and vascular health.…”

Section: Discussionmentioning

confidence: 99%

TNF-α impairs endothelial function in adipose tissue resistance arteries of mice with diet-induced obesity

Donato

Henson

Morgan

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

; P Ͻ 0.05) and the homeostatic model assessment (HF, 64.1 Ϯ 4.3 vs. NC, 85.7 Ϯ 6.4; P ϭ 0.05). HF diet-induced metabolic dysfunction was concomitant with a proinflammatory eWAT phenotype characterized by greater macrophage infiltration (HF, 3.9 Ϯ 0.8 vs. NC, 0.8 Ϯ 0.4%; P ϭ 0.01) and TNF-␣ (HF, 22.6 Ϯ 4.3 vs. NC, 11.4 Ϯ 2.5 pg/dl; P Ͻ 0.05) and was associated with resistance artery dysfunction, evidenced by impaired endotheliumdependent dilation (EDD) (maximal dilation; HF, 49.2 Ϯ 10.7 vs. NC, 92.4 Ϯ 1.4%; P Ͻ 0.01). Inhibition of nitric oxide (NO) synthase by N -nitro-L-arginine methyl ester (L-NAME) reduced dilation in NC (28.9 Ϯ 6.3%; P Ͻ 0.01)-and tended to reduce dilation in HF (29.8 Ϯ 9.9%; P ϭ 0.07)-fed mice, eliminating the differences in eWAT artery EDD between NC-and HF-fed mice, indicative of reduced NO bioavailability in eWAT resistance arteries after HF feeding. In vitro treatment of excised eWAT arteries with recombinant TNF-␣ (rTNF) impaired EDD (P Ͻ 0.01) in NC (59.7 Ϯ 10.9%)-but not HF (59.0 Ϯ 9.3%)-fed mice. L-NAME reduced EDD in rTNF-treated arteries from both NC (21.9 Ϯ 6.4%)-and HF (29.1 Ϯ 9.2%)-fed mice (both P Ͻ 0.01). In vitro treatment of arteries with a neutralizing antibody against TNF-␣ (abTNF) improved EDD in HF (88.2 Ϯ 4.6%; P ϭ 0.05)-fed mice but was without effect on maximal dilation in NC (89.0 Ϯ 5.1%)-fed mice. L-NAME reduced EDD in abTNF-treated arteries from both NC (25.4 Ϯ 7.5%)-and HF (27

show abstract

In obesity and weight loss, all roads lead to the mighty macrophage

Cited by 30 publications

References 20 publications

Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice

Isolated exopolysaccharides from Lactobacillus rhamnosus GG alleviated adipogenesis mediated by TLR2 in mice

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

TNF-α impairs endothelial function in adipose tissue resistance arteries of mice with diet-induced obesity

Contact Info

Product

Resources

About