Sexually dimorphic hepatic genes associated with NAFLD

Gene Function (s) Model (s) Used Female Male Effect (s)
JNK Transcription factor; regulate fatty acid oxidation; improve insulin sensitivity SHROB Rats ↑↑ Less severe steatosis in females
AMPK Transcription factor; regulate fatty acid oxidation; improve insulin sensitivity SHROB Rats ↑↑ Less severe steatosis in females
CD36 Receptor; promotes fatty acid uptake into muscle and adipose tissues; fatty acid transport, β-oxidation SHROB Rats; FXR-deficient mice; C57BL6/J HFD Mice ↑↑ Less severe steatosis in females
PPARγ Transcription factor; activates SREBP-1c, a master transcription factor that promotes de novo lipid synthesis (DNL) SHROB Rats ↑↑ More severe steatosis and inflammation in males
PNPLA3 Enzyme; involved in the accumulation of lipid droplets; esterification SHROB Rats; C57BL6/J HFD Mice ↑↑ More severe steatosis and inflammation in males
AQP7 The main channel in facilitating the release of lipolytic glycerol from adipocytes C57BL/6 HFD mice, streptozotocin-induced DM rats ↑↑ Increase plasma glycerol levels in both sexes
AQP9 The principal facilitative pathway in liver uptake of glycerol C57BL/6 HFD mice, streptozotocin-induced DM rats ↓↓
(Expression and glycerol permeability)
Less severe steatosis and hyperglycemia in females

SHROB: obese spontaneously hypertensive; ↑ increased; ↑↑ highly increased; ↓ decreased; ↓↓ highly decreased