Diabetes, inflammation, and the adiponectin paradox: Therapeutic targets in SARS-CoV-2

Ho, Gilbert; Ali, Alysha; Takamatsu, Yoshiki; Wada, Ryoko; Masliah, Eliezer; Hashimoto, Makoto

doi:10.1016/j.drudis.2021.03.013

Cited by 16 publications

(19 citation statements)

References 65 publications

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“…Many studies have shown that the accumulation of DAMPs is one of the important causes of aging-related damage [25]. TLR4 is a predominant DAMP sensor that has been proven to mediate inflammation in many cell types.…”

Section: Discussionmentioning

confidence: 99%

Loss of toll-like receptor 4 ameliorates cardiovascular dysfunction in aged mice

Liu

Chu

2021

Immun Ageing

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Background Toll-like receptor 4 (TLR4) is a pattern recognition receptor of the innate immune system. TLR4 contributes to many aging-related chronic diseases. However, whether TLR4 is involved in cardiovascular injury during the aging process has not been investigated. Methods The effects of TLR4 on the cardiovascular system of aged mice were investigated in TLR4−/− mice. An intraperitoneal glucose tolerance test (IPGTT) and insulin sensitivity test (IST) were conducted to evaluate global insulin sensitivity. Echocardiography was used to measure cardiac structure and performance. An isolated artery ring assay was used to measure the vasodilator function of the thoracic aorta. The inflammatory response was reflected by the serum concentration of cytokines. Results TLR4 expression increased in the hearts and aortas of mice in an age-dependent manner. Loss of TLR4 increased insulin sensitivity in aged mice. Moreover, loss of TLR4 improved cardiac performance and endothelium-dependent vascular relaxation in aged mice. Importantly, the increases in serum inflammatory cytokines and oxidative stress in the heart and aorta were also inhibited by TLR4 deficiency. Conclusion In summary, loss of TLR4 improved cardiac performance and endothelium-dependent vascular relaxation in aged mice. The reduced inflammatory responses and oxidative stress may be the reason for the protective effects of TLR4 deficiency during aging. Our study indicates that targeting TLR4 is a potential therapeutic strategy for preventing aging-related cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Loss of toll-like receptor 4 ameliorates cardiovascular dysfunction in aged mice

Liu

Chu

2021

Immun Ageing

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“…Moreover, a link between 'adiponectin paradox' and SARSCoV2 infection and its chronic complications has also been demonstrated lately [221]. Curiously, antagonistic pleiotropy was found.…”

Section: Facets Of Adiponectin Paradoxmentioning

confidence: 98%

“…Accordingly, SARSCoV2 may aug ment both chronic inflammation and adiponectin serum levels and this plays a beneficial role contributing to more efficient combating acute infection in younger ages rep resenting a kind of hormesis. Conversely, in aging popu lation SARSCoV2 induction of 'adiponectin paradox' is detrimental [221].…”

Section: Facets Of Adiponectin Paradoxmentioning

confidence: 99%

Adiponectin: a pleiotropic hormone with multifaceted roles

Shklyaev

Мельниченко

Волеводз

et al. 2021

Probl Endokrinol (Mosk)

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Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called ‘adiponectin paradox’. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.

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“…Ho et. al found that aging and comorbidities augment risk the of ARDS in COVID-19, and SARS-CoV-2-induced inflammation can cause IR and APN paradox ( Ho et al, 2021 ). Therefore, inhibition of APN paradox-mediated inflammation could be beneficial in this regard ( Ho et al, 2021 ).…”

Section: Role Of Apn In Sars-cov-2 Infectionmentioning

confidence: 99%

The potential molecular implications of adiponectin in the evolution of SARS-CoV-2: Inbuilt tendency

Al-Kuraishy

Al-Gareeb

Bungău

et al. 2022

Journal of King Saud University - Science

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Diabetes, inflammation, and the adiponectin paradox: Therapeutic targets in SARS-CoV-2

Abstract: Graphical abstract

Cited by 16 publications

References 65 publications

Loss of toll-like receptor 4 ameliorates cardiovascular dysfunction in aged mice

Loss of toll-like receptor 4 ameliorates cardiovascular dysfunction in aged mice

Adiponectin: a pleiotropic hormone with multifaceted roles

The potential molecular implications of adiponectin in the evolution of SARS-CoV-2: Inbuilt tendency

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