Magnesium accumulation upon cyclin M4 silencing activates microsomal triglyceride transfer protein improving NASH.

ABSTRACT:

Background & aims

Perturbations of intracellular magnesium (Mg²⁺) homeostasis have implications for cell physiology. The cyclin M family, CNNM, perform key functions in the transport of Mg²⁺ across cell membranes. Herein, we aimed to elucidate the role of CNNM4 in the development of non-alcoholic steatohepatitis (NASH).

Methods

Serum Mg²⁺ levels and hepatic CNNM4 expression were characterised in clinical samples. Primary hepatocytes were cultured under methionine and choline deprivation. A 0.1% methionine and choline-deficient diet, or a choline-deficient high-fat diet were used to induce NASH in our in vivo rodent models. Cnnm4 was silenced using siRNA, in vitro with DharmaFECT and in vivo with Invivofectamine® or conjugated to N-acetylgalac

SUBMITTER: Simon J 

PROVIDER: S-EPMC8217299 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature