Chronic helminth infection and helminth‐derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice

Hussaarts, Leonie; García-Tardón, Noemí; Beek, Lianne van; Heemskerk, Mattijs M.; Haeberlein, Simone; Zon, Gerard C. van der; Ozir‐Fazalalikhan, Arifa; Berbée, Jimmy F.P.; Dijk, Ko Willems van; Harmelen, Vanessa van; Yazdanbakhsh, Maria; Guigas, Bruno

doi:10.1096/fj.14-266239

Cited by 173 publications

(226 citation statements)

References 54 publications

Supporting

Mentioning

203

Contrasting

Unclassified

Order By: Relevance

“…These observations suggest that factors other than M2 macrophage accumulation contribute to changes in glycemic status in these discordant situations. One potential trigger of metabolic improvement is the marked Th2 immune response (27) induced by helminths (26). We did not detect increased IL-4, -13, and -15 Th2 cytokine gene expression and release in WAT after 7 gavages (data not shown), suggesting that type 2 immune response is not a prominent consequence of t10,c12-CLA administration, at least for the short period tested in our current study.…”

Section: Discussionmentioning

confidence: 54%

Adipose tissue adaptive response totrans‐10,cis‐12‐conjugated linoleic acid engages alternatively activated M2 macrophages

et al. 2015

View full text Add to dashboard Cite

In mice, nutritional supplementation with the trans-10,cis-12 isomer of linoleic acid (t10,c12-CLA) promotes lipoatrophy, hyperinsulinemia, and macrophage infiltration in white adipose tissue (WAT). We explored the dynamics of these interrelated responses over 2 consecutive 7 d periods of t10,c12-CLA administration and withdrawal. t10,c12-CLA down-regulated lipogenic and lipolytic gene expression and increased collagen deposition, but with no evidence of cross-linking. An abundant CD45 + cell infiltrate, comprising prominently CD206 + CD11c 2 macrophages, was found in WAT in association with an anti-inflammatory gene signature. Infiltration of natural killer (NK) and dendritic cells contributed to WAT's innate immune response to t10,c12-CLA. Less abundant adaptive immune cells colonized WAT, including B, NK T, gd T, and ab T cells. By contrast, T-regulatory cell abundance was not affected. Interruption of treatment allowed recovery of WAT mass and normalization of insulinemia, coincident with regain of WAT homeostasis owing to a coordinated reversion of genic, structural, and immune deregulations. These data revealed a striking resilience of WAT after a short-term metabolic injury induced by t10,c12-CLA, which relies on alternatively activated M2 macrophage engagement. In addition, the temporal links between variations in WAT alterations and insulinemia upon t10,c12-CLA manipulation strengthen the view that WAT dysfunctional status is critically involved in altered glucose homeostasis.-Pini, M., Touch, S., Poirier, H., Dalmas, E., Niot, I., Rouault, C., Druart, C., Delzenne, N., Clément, K., André, S., Guerre-Millo, M. Adipose tissue adaptive response to trans-10,cis-12-conjugated linoleic acid engages alternatively activated M2 macrophages. It is broadly agreed that accumulation of proinflammatory macrophages is a key component of white adipose tissue (WAT) response to nutrient overload in obesity. Through the release of an array of proinflammatory chemokines and cytokines, macrophages are thought to perpetuate and propagate inflammation in WAT, leading eventually to a chronic pathologic state. Although opposite in terms of excess vs. deficiency of fat mass, obesity and lipodystrophy share common WAT alterations, including inflammation and macrophage infiltration, as shown in several lipodystrophic mouse models (1-3) and in patients with HIV-associated lipodystrophy (4-6). Enhanced extracellular matrix (ECM) deposition and fibrosis are additional signatures of WAT pathology in both conditions (4,7,8). These local alterations are accompanied by systemic inflammation and insulin resistance, the most prevalent outcomes of WAT dysfunction common to obesity and lipodystrophy (9).The time frame necessary for WAT macrophage accumulation and insulin resistance to occur is usually long, ranging from months in mice fed a high-fat diet to years in obese humans. Conversely, caloric restriction attenuates WAT inflammation and improves glycemic status in obese humans and mice after prolonged periods of weight reducti...

show abstract

Section: Discussionmentioning

confidence: 54%

Adipose tissue adaptive response totrans‐10,cis‐12‐conjugated linoleic acid engages alternatively activated M2 macrophages

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The lack of changes in body weight and adipose tissue mass in L.s. -infected and LsAg-treated DIO mice in comparison to previous studies using N. brasiliensis [3] and Schistosoma mansoni [47] may also be linked to differences in parasite locations in the host and the compositions of antigens that were used. Adult L.s.…”

Section: Discussionmentioning

confidence: 88%

“…Accordingly, our PCR array results indicated for example the induction of IFNγ with LsAg treatment. Thus, identification of an active component within LsAg may further improve the protective effect on diet-induced glucose intolerance which may resemble the protective effect observed with S. mansoni soluble egg antigens [47], which is known to be a strong inducer of type 2 immune responses.…”

Section: Discussionmentioning

confidence: 99%

Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice

et al. 2016

View full text Add to dashboard Cite

Helminths induce type 2 immune responses and establish an anti-inflammatory milieu in their hosts. This immunomodulation was previously shown to improve diet-induced insulin resistance which is linked to chronic inflammation. In the current study, we demonstrate that infection with the filarial nematode Litomosoides sigmodontis increased the eosinophil number and alternatively activated macrophage abundance within epididymal adipose tissue (EAT) and improved glucose tolerance in diet-induced obese mice in an eosinophil-dependent manner. L. sigmodontis antigen (LsAg) administration neither altered the body weight of animals nor adipose tissue mass or adipocyte size, but it triggered type 2 immune responses, eosinophils, alternatively activated macrophages, and type 2 innate lymphoid cells in EAT. Improvement in glucose tolerance by LsAg treatment remained even in the absence of Foxp3+ regulatory T cells. Furthermore, PCR array results revealed that LsAg treatment reduced inflammatory immune responses and increased the expression of genes related to insulin signaling (Glut4, Pde3b, Pik3r1, and Hk2) and fatty acid uptake (Fabp4 and Lpl). Our investigation demonstrates that L. sigmodontis infection and LsAg administration reduce diet-induced EAT inflammation and improve glucose tolerance. Helminth-derived products may, therefore, offer new options to improve insulin sensitivity, while loss of helminth infections in developing and developed countries may contribute to the recent increase in the prevalence of type 2 diabetes.

show abstract

“…For example, chronic helminth infection in mice increases white adipose tissue eosinophils and M2 macrophages and improves glucose uptake and insulin sensitivity 54 . Further studies elucidating the mechanisms behind eosinophil activation and its beneficial metabolic effects are warranted as they may reveal new drug targets.…”

Section: Macrophage Functions In Lean Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

View full text Add to dashboard Cite

Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

show abstract

Chronic helminth infection and helminth‐derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice

Cited by 173 publications

References 54 publications

Adipose tissue adaptive response totrans‐10,cis‐12‐conjugated linoleic acid engages alternatively activated M2 macrophages

Adipose tissue adaptive response totrans‐10,cis‐12‐conjugated linoleic acid engages alternatively activated M2 macrophages

Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice

Macrophage functions in lean and obese adipose tissue

Contact Info

Product

Resources

About