Youling Hao, Nadia Romp, Stefan Havik, Aldo Grefhorst, Max Nieuwdorp, Elena Rampanelli
Anaerobutyricum soehngenii (A. soehngenii) has been shown to exert beneficial effects on glucose metabolism. In a clinical research study, we discovered that administration of A. soehngenii specifically upregulates Reg1B expression in the human duodenal mucosa, and this upregulation was associated with a reduction in glycemic variability. To further investigate this relationship, we explored the interplay between A. soehngenii and intestinal Reg1B using a murine model of diet-induced obesity (DIO).
We found that heat-inactivated A. soehngenii upregulates the expression of endogenous Reg1B and promotes insulin sensitivity in obese mice. To establish the role of intestinal Reg1B, we next administered Reg1B in the gut of DIO mice and disclosed that Reg1B improved insulin sensitivity and reduced hepatic inflammation and steatosis . Mechanistically, Reg1B enhanced the expression of molecules involved in mitochondrial oxidative metabolism and fatty acid oxidation in the liver. Furthermore, within the inguinal white adipose tissue (WAT), Reg1B administration increased the expression of key players in oxidative mitochondrial metabolism and markers of adipose tissue browning.
In conclusion, our findings suggest that A. soehngenii may confer metabolic benefits through the upregulation of Reg1B, which in turn enhances insulin sensitivity and lipolysis. Hence, Reg1B has therapeutic potential in counteracting diabetes and obesity.
Key word: Reg1B, insulin signaling, liver steatosis, microbiota, MASLD, diabetes
Author list
y.hao@amsterdamumc.nl Amsterdam UMC location Academic Medical Center, Department of Experimental Vascular Medicine, Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, The Netherlands;
n.romp@amsterdamumc.nl Amsterdam UMC location Academic Medical Center, Department of Experimental Vascular Medicine, Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, The Netherlands;
s.r.havik@amsterdamumc.nl Amsterdam UMC location Academic Medical Center, Department of Vascular Medicine, Amsterdam, The Netherlands;
a.grefhorst@amsterdamumc.nl Amsterdam UMC location Academic Medical Center, Department of Experimental Vascular Medicine, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, The Netherlands;
m.nieuwdorp@amsterdamumc.nl Amsterdam UMC location Academic Medical Center, Department of Vascular Medicine ,Amsterdam, The Netherlands;
e.rampanelli@amsterdamumc.nl Amsterdam UMC location Academic Medical Center, Department of Experimental Vascular Medicine, Amsterdam Institute for Immunology and Infectious Diseases , Amsterdam, The Netherlands