Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin

Mahlangu, Thabsile; Dludla, Phiwayinkosi V.; Mxinwa, Vuyolwethu; Mkandla, Zibusiso; Tiano, Luca; Louw, Johan; Mutize, Tinashe; Nyambuya, Tawanda M.; Nkambule, Bongani B.

doi:10.1016/j.cyto.2020.154999

Cited by 13 publications

(9 citation statements)

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“…The reported results are consistent with our previous results of HFD-induced Glc intolerance. 16 , 20 In our study impaired Glc metabolism and elevated insulin levels were observed in the HFD group and these were independent of mass gain following 8 wk of HFD-feeding. Notably, elevated levels of ILC2 activity is associated with impaired Glc tolerance and dysregulated cholesterol in patients with metabolic syndrome.…”

Section: Discussionsupporting

confidence: 52%

Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet

et al. 2021

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Impaired Glc tolerance and hyperinsulinemia are a hallmark of type 2 diabetes (T2D) and are associated with an altered innate and adaptive immune response. In this study, we used a high-fat diet (HFD)-induced model of pre-diabetes to explore the pathological implications of altered innate lymphoid cell (ILC) profiles in a state of impaired Glc tolerance. Sixteen male C57BL/6 mice were randomized to receive two experimental diets ( n = 8 per group), low-fat (LFD), and HFD for 8–13 wk. We evaluated the levels of circulating innate lymphoid cells and their respective cytokines following HFD-feeding. The HFD group had impaired Glc tolerance, elevated insulin levels, and increased total cholesterol levels. Notably, the levels of circulating ILC1s were elevated following 13 wk of HFD-feeding. Moreover, the levels of TNF-α were decreased, but there were no changes in IFN-γ levels. Lastly, the levels of circulating ILC2s and ILC3s were comparable between the HFD and LFD group. The findings demonstrated that short-term HFD-feeding increases postprandial blood Glc, total cholesterol and insulin levels. However, the metabolic changes did not alter ILC2 and ILC3 levels and their respective cytokine profiles.

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Section: Discussionsupporting

confidence: 52%

Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet

et al. 2021

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“…White et al 42 In this study, we chose 1 mg/kg/d and 10 mg/kg/d as the doses of AS for treatment, based on the usual doses of AS utilized in prior studies. [48][49][50][51] According to the findings of this study, both doses of AS…”

Section: Discussionmentioning

confidence: 52%

“…In this study, we chose 1 mg/kg/d and 10 mg/kg/d as the doses of AS for treatment, based on the usual doses of AS utilized in prior studies 48–51 . According to the findings of this study, both doses of AS alleviated cartilage degeneration in the DMM mouse model, indicating that AS has an anti‐OA effect in the DMM mouse model.…”

Section: Discussionmentioning

confidence: 99%

Aspirin reverses inflammatory suppression of chondrogenesis by stabilizing YAP

et al. 2022

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Bone marrow mesenchymal stem cells (BMMSCs) transplantation methods are promising candidates for osteoarthritis (OA) treatment. However, inflammatory factors (such as TNF-α) that occur at cell transplantation sites are critical factors that impair the effectiveness of the treatment. Previous studies have shown that aspirin (AS) had a regulatory role in stem cell differentiation. However, little is known about the role of AS on the chondrogenesis of BMMSCs. The purpose of this study is to explore the protective role of AS against the negative effects of TNF-α on BMMSC chondrogenesis. In this study, we investigated the effects of AS and TNF-α on BMMSCs chondrogenesis by performing the Alcian Blue staining, safranin O-fast green staining, haematoxylin and eosin staining, and immunohistochemical staining, as well as realtime RT-PCR and western blot assays. Our results demonstrated that TNF-α inhibited chondrogenic differentiation of BMMSCs by disrupting the balance of cartilage metabolism and promoting oxidative stress in BMMSCs, while AS treatment attenuated these effects. Furthermore, a detailed molecular mechanistic analysis indicated that Yes-associated protein (YAP) played a critical regulatory role in this process. In addition, AS treatment mitigated the progression of cartilage degeneration in a mouse destabilization of the medial meniscus (DMM) model. AS alleviated the inhibitory effect of TNF-α on chondrogenesis of BMMSCs by stabilizing YAP, which may provide new therapeutic strategies for OA treatment.

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“…[ 103 ]. In a mouse model, a high cholesterol diet increased the levels of Th2 cytokine and T reg, suggesting that cholesterol may be indirectly involved in Th2 cell or Treg differentiation [ 104 , 105 ]. Th2 cells are the primary players in the pathogenesis of allergies.…”

Section: The Impact Of Cholesterol and Oxysterols On Immune Cellsmentioning

confidence: 99%

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

Yanagisawa

Asai

et al. 2022

IJMS

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Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as β-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.

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Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin

Cited by 13 publications

References 30 publications

Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet

Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet

Aspirin reverses inflammatory suppression of chondrogenesis by stabilizing YAP

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

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