Cynandione A causes a dynamic change in SIRT1 nuclear trafficking via PKA signaling and beige adipocyte differentiation in 3T3-L1 cells

Sawamoto, Atsushi; Kanazaki, Asami; Nakanishi, Mahito; Amakura, Yoshiaki; Yoshimura, Manabu; Uchiyama, Nahoko; Hakamatsuka, Takashi; Okuyama, Satoshi; Nakajima, Miki

doi:10.1016/j.ejphar.2021.174382

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…32 We have previously reported a practical approach for screening healthy compounds with metabolism-improving actions. 33 Using this screening method, we have identified phytochemicals, including cynandione A 34,35 and N-caffeoyltryptophan, 36 with beneficial effects on metabolism. In a preliminary experiment, we applied this screening method for DR and found a candidate compound, tipepidine (TP; chemically 3-[di-2-thienylmethylene]-1-methylpiperid ine) (Figure 1A), a non-narcotic antitussive drug, which has been used for more than 60 years since its approval in Japan in 1959, and its safety for use in all age groups is well established.…”

Section: Introductionmentioning

confidence: 99%

Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high‐fat diet‐induced obese mice

Sawamoto,

Okada,

Matsuoka

et al. 2024

The FASEB Journal

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Tipepidine (3‐[di‐2‐thienylmethylene]‐1‐methylpiperidine) (TP) is a non‐narcotic antitussive used in Japan. Recently, the potential application of TP in the treatment of neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder, has been suggested; however, its functions in energy metabolism are unknown. Here, we demonstrate that TP exhibits a metabolism‐improving action. The administration of TP reduced high‐fat diet‐induced body weight gain in mice and lipid accumulation in the liver and increased the weight of epididymal white adipose tissue (eWAT) in diet‐induced obese (DIO) mice. Furthermore, TP inhibited obesity‐induced fibrosis in the eWAT. We also found that TP induced AMP‐activated protein kinase (AMPK) activation in the eWAT of DIO mice and 3T3‐L1 cells. TP‐induced AMPK activation was abrogated by the transfection of liver kinase B1 siRNA in 3T3‐L1 cells. The metabolic effects of TP were almost equivalent to those of metformin, an AMPK activator that is used as a first‐line antidiabetic drug. In summary, TP is a potent AMPK activator, suggesting its novel role as an antidiabetic drug owing to its antifibrotic effect on adipose tissues.

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Section: Introductionmentioning

confidence: 99%

Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high‐fat diet‐induced obese mice

Sawamoto,

Okada,

Matsuoka

et al. 2024

The FASEB Journal

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An Investigation of Substances Influencing Adipocyte Function

Sawamoto

2024

YAKUGAKU ZASSHI

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Adipose tissue plays a central metabolic role in systemic energy metabolism via nutrient exchange and secretion of adipose-derived hormones and cytokines. Adipose tissue dysfunction increases the risk of developing conditions, including type 2 diabetes, coronary artery disease, stroke, and cancer, ultimately shortening healthy lifespan. Maintaining adipose tissue functions has recently garnered attention as a means to extend healthy life expectancy. We previously developed a T-cell activation-inhibitory assay, which facilitates efficient selection of candidate substances for extending healthy lifespan. Using this assay, we identified two candidate substances: Cynandione A (CA), a major component of Cynanchum wilfordii, and N-caffeoyltryptophan (NCT) found in coffee. This review summarizes recent findings regarding the effect of CA and NCT on adipocyte (the primary cells in adipose tissue) function, and their potential contribution to extending healthy life expectancy.

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Cynandione A causes a dynamic change in SIRT1 nuclear trafficking via PKA signaling and beige adipocyte differentiation in 3T3-L1 cells

Cited by 2 publications

References 47 publications

Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high‐fat diet‐induced obese mice

Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high‐fat diet‐induced obese mice

An Investigation of Substances Influencing Adipocyte Function

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