Geniposide suppresses thermogenesis via regulating PKA catalytic subunit in adipocytes. (December 2021)

• Record Type: Journal Article
• Authors: Li, Yan; Zhang, Kuiliang; Liu, Jinxin; Liu, Shengnan; Nie, Chenzhipeng; Yan, Ying; Guan, Yanming; Fan, Mingcong; Qian, Haifeng; Ying, Hao; Wang, Li
• Is Part Of: Toxicology. Volume 464(2021)
• Publication Date: 2021-12
• Subjects: AKAPs protein kinase A anchoring proteins -- AKT serine-threonine kinase -- AMPK AMP (adenosine monophosphate)-activated protein kinase -- ATF2 activating transcription factor 2 -- ATP adenosine triphosphate -- BAC brown adipocytes -- BAT brown adipose tissue -- cAMP cyclic adenosine monophosphate -- CIDEA cell death-inducing DNA fragmentation factor α-like effector A -- CREB cAMP-response element binding protein -- DEX dexamethasone -- DIO2 iodothyronine deiodinase 2 -- DMEM Dulbecco's modified Eagle's medium -- DMSO dimethyl sulfoxide -- ELVOL3 long-chain fatty acid elongase 3 -- ERK extracellular signal-related kinase -- GFP green fluorescence protein -- H&E Hematoxylin and Eosin -- HEK293T human embryonic kidney 293T -- iBAT interscapular brown adipose tissue -- IBMX 3-isobutyl-1-methylxanthine -- iWAT inguinal white adipose tissue -- MAPK mitogen-activated protein kinase -- OCR oxygen consumption rate -- PGC1α peroxisome proliferator activated receptor-γ coactivator 1α -- PKA protein kinase A -- PKA C PKA catalytic subunit -- PKA R PKA regulatory subunit -- PRDM16 PR domain-containing protein 16 -- qRT-PCR quantitative real-time polymerase chain reaction -- SEM standard error mean -- Sirt1 sirtuin 1 -- T3 triiodothyronine -- UCP1 uncoupling protein 1 -- WAT white adipose tissue; Geniposide -- Adipose -- Thermogenesis -- Uncoupling protein 1 -- Protein kinase; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2021.153014
• Languages: English
• ISSNs: 0300-483X

Abstract

Graphical abstract: Highlights: Geniposide suppresses the browning processing of adipocytes. Geniposide treatment reduces body temperature and cold tolerance of mice. PKA signaling is required for the inhibition of geniposide on adipocyte browning. Abstract: Geniposide has been widely found to ameliorate many metabolic diseases. The recruitment and activation of brown/beige adipocytes are effective and promising methods for counteracting obesity and related diseases. However, the effect of geniposide on thermogenesis of adipocytes and its underlying mechanism have not yet been investigated. Here, we demonstrate that geniposide (25 mg/kg) reduces body temperature and cold tolerance of mice via suppressing thermogenic genes in interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT). Consistently, geniposide (20 mg/mL) suppresses thermogenic capacity of adipocytes (brown adipocytes and 3T3L1 preadipocyte cells) in vitro. Mechanistically, geniposide reduces the level of protein kinase A (PKA) catalytic subunit and further suppresses transcription activity and protein stability of uncoupling protein 1 (UCP1), leading to reduction of thermogenic capacity in adipocytes. Moreover, pharmacological PKA activation reverses geniposide-induced UCP1 inhibition, which indicated that geniposide suppresses thermogenesis of adipocytes via regulating PKA signaling. Together, our findings suggest that geniposide is an inhibitor of fat thermogenesis, establishing a novel function characteristic of geniposide.