Cardiovascular disease risk factors and lifestyle modification strategies after pediatric kidney transplantation: what are we dealing with, and what can we target?

Kidney transplantation in pediatric patients can lead to partial improvement of some of the cardiometabolic parameters that increase the risk for cardiovascular disease (CVD) in patients with chronic kidney disease. However, even after restoration of kidney function, transplant recipients remain at risk for CVD due to the continual presence of traditional and non-traditional risk factors, including the side effects of immunosuppression and chronic inflammation. This educational review describes the prevalence of CVD risk factors in pediatric kidney transplant recipients and presents available evidence for therapeutic lifestyle changes and other non-pharmacologic strategies that can be used to improve traditional and modifiable CVD risk factors.

DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1.

Fructose over-consumption contributes to the development of liver steatosis in part by stimulating ChREBPα-driven de novo lipogenesis. However, the mechanisms by which fructose activates ChREBP pathway remain largely undefined. Here we performed affinity purification of ChREBPα followed by mass spectrometry and identified DDB1 as a novel interaction protein of ChREBPα in the presence of fructose.

The hepatic BMAL1/AKT/lipogenesis axis protects against alcoholic liver disease in mice via promoting PPARα pathway.

Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially, hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show that the circadian clock protein BMAL1 in hepatocytes is both necessary and sufficient to protect mice from ALD.

DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver.

Targeted protein degradation through ubiquitination is an important step in the regulation of glucose metabolism. Here, we present evidence that the DDB1-CUL4A ubiquitin E3 ligase functions as a novel metabolic regulator that promotes FOXO1-driven hepatic gluconeogenesis. In vivo, hepatocyte-specific deletion leads to impaired hepatic gluconeogenesis in the mouse liver but protects mice from high-fat diet-induced hyperglycemia.