Mechanosensitive Ion Channel Piezo1 Regulates Diet-Induced Adipose Inflammation and Systemic Insulin Resistance

Abstract

Adipocytes function as an energy buffer and undergo significant size and volume changes in response to nutritional cues. This adipocyte plasticity is important for systemic lipid metabolism and insulin sensitivity. Accompanying the adipocyte size and volume changes, the mechanical pressure against cell membrane also changes. However, the role that mechanical pressure plays in lipid metabolism and insulin sensitivity remains to be elucidated. Here we show that Piezo1, a mechanically-activated cation channel stimulated by membrane tension and stretch, was highly expressed in adipocytes. Adipose Piezo1 expression was increased in obese mice. Adipose-specific piezo1 knockout mice (adipose-Piezo1 −/− ) developed insulin resistance, especially when challenged with a high-fat diet (HFD). Perigonadal white adipose tissue (pgWAT) weight was reduced while pro-inflammatory and lipolysis genes were increased in the pgWAT of HFD-fed adipose-Piezo1 −/− mice. The adipose-Piezo1 −/− mice also developed hepatic steatosis with elevated expression of fatty acid synthesis genes. In cultured adipocytes, Piezo1 activation decreased, while Piezo1 inhibition elevated pro-inflammatory gene expression. TLR4 antagonist TAK-242 abolished adipocyte inflammation induced by Piezo1 inhibition. Thus, adipose Piezo1 may serve as an adaptive mechanism for adipocyte plasticity restraining pro-inflammatory response in obesity.

Low HbA1c With Normal Hemoglobin in a Diabetes Patient Caused by PIEZO1 Gene Variant: A Case Report

“…For this patient, the decrease in fasting and post-prandial insulin level was not consistent with typical T2DM, suggesting that there may be a specific relationship between DHS and the onset of diabetes mellitus. Recent studies indicated that PIEZO1 is a mechanically activated ion channel that might mediate pressure-induced pancreatitis and regulate diet-induced systemic insulin resistance (23,24). However, there was no evidence proving the mutation on the PIEZO1 gene could directly affect the onset of diabetes.…”

Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1

“…Histone protein was extracted using the EpiQuik Total Histone Extraction Kit from EpiGentek. Western blot was performed following a standard protocol ( 14 , 74 , 85 ). For IP, protein lysates were incubated with indicated antibodies at 4°C overnight.…”

“…EpiGentek. Western blot was performed following a standard protocol (14,74,85). For immunoprecipitation, protein lysates were incubated with indicated antibodies at 4 o C overnight.…”

“…Liver lipids were extracted using chloroform/methanol (2:1) as a solvent. Total triglyceride contents of the liver were determined by an enzymatic method (Stanbio Laboratory) (14,85).…”

Yoda1 Activates Piezo1 in Vitro to Simulate the Upregulation of Piezo1 in the Infected Brain: Piezo1 Participates in the Immune Activation of Microglia.

“…The Piezo1 channel is a newly discovered mechanosensitive ion channel that gives cells the ability to convert mechanical signals into intracellular signals [4]. A large amount of evidence supports that Piezo1 is involved in regulating in ammation induced by mechanical stress [5][6][7][8]. Piezo1 is mainly located in the plasma membrane, and it has also been reported in the endoplasmic reticulum, cytoplasmic compartment and nuclear envelope near the nucleus [9][10][11][12][13].…”