Mechanisms of Malnutrition in Cirrhosis With Portosystemic Shunting

Cirrhosis is characterized by loss of muscle as well as fat mass, which increases morbidity
and mortality before, during, and after liver transplantation. A common mechanism for the
reduced muscle and fat mass in cirrhosis is an increased expression of the TGF (transforming
growth factor)beta superfamily member, myostatin, in the muscle and adipose tissue. The
present study will examine the expression of myostatin, its receptor and intracellular
signaling pathways in the skeletal muscle and mesenteric adipose tissue in cirrhotic patients
undergoing liver transplantation as compared to healthy controls undergoing planned abdominal
surgery. 16 cirrhotic patients will be identified from the transplant list, and 16 healthy
controls from outpatient surgery lists. Nutritional assessment will be performed, including
anthropometry (triceps skinfold thickness, mid arm circumference), dual energy x-ray
absorptiometry (DEXA), and bioelectrical impedance analysis (BIA). Rectus abdominis muscle
tissue and omental fat tissue will be harvested in the operating room, and the expression of
signaling proteins involved in skeletal muscle protein synthesis will be quantified. The
investigator will also quantify the expression of genes involved in lipolysis and lipid
synthesis. The investigator anticipates that the expression of myostatin will be higher in
the skeletal muscle and adipose tissue of cirrhotics as compared to controls. There will be a
reduction in the expression of the signaling proteins that regulate skeletal muscle protein
synthesis, as well as the expression of genes regulating lipogenesis. The increased
expression of myostatin will also correlate with reduced anthropometric and DEXA measurements
of lean body mass and fat mass.