Premium
A model of clinical inactivity with hypercortisolemia and hypocaloric diet induces peripheral insulin resistance and increases intramuscular fat
Author(s) -
Cree Melanie G.,
Ferrando Arny,
Newcomer Brad R.,
Aarsland Asle,
Wolfe Robert R.,
PaddonJones Douglas
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1225.2
Subject(s) - insulin resistance , medicine , endocrinology , insulin , glucose clamp technique , hypercortisolemia , insulin sensitivity , hydrocortisone
Many clinical conditions necessitate extended periods of bed rest and are characterized by a hypocaloric diet, hypercortisolemia and the rapid development of insulin resistance. Reduced insulin sensitivity has been linked to increased intracellular fat accumulation in the muscle and liver. However, it is unclear if tissue lipids increase during inactivity with a hypocaloric diet. To mimic a common clinical paradigm, we studied healthy volunteers before and after 14 days of bed rest with induced hypercortisolemia (20–24mg/dL) via oral hydrocortisone sodium succinate administration and hypocaloric diet (80% estimated daily requirement). Insulin sensitivity across the leg was assessed via blood sampling performed in association with a locally induced, hyperinsulinemic‐euglycemic clamp (0.15 mU/min/100ml leg). Intramuscular and liver fat were measured with magnetic resonance spectroscopy. Following bed rest, there was a decrease in insulin sensitivity across the leg (Pre: 5.82±0.19; Post: 4.21±0.33 mg/kg.leg/min; P=0.04) and increase in Intramuscular triglycerides (Pre: 0.13±0.02; Post: 0.18±0.02) (signal area of fat/signal area of standard; P=0.02). Liver triglycerides did not change (Pre: 0.10±0.02; Post: 0.11±0.02). Femoral glycerol and free fatty acid concentrations decreased with increasing insulin concentrations, but did not reach statistical significance following bed rest. This study demonstrates that insulin resistance is induced and intramuscular triglycerides increase during a model of clinical inactivity, despite a hypo‐caloric diet and the absence of detectable changes in plasma lipids or hepatic fat.