2011 ADA Posters 1261-2041.indd - Diabetes

Integrated Physiology/
Obesity
POSTERS
novel long-term model indicates that diabetes contributes to progression
from NASH to more end-stage liver disease. Subsequent studies will further
defi ne molecular mechanisms of this process. Supported by NHMRC of
Australia Project Grant #632822.
Supported by: NHMRC of Australia Project Grant No. 632822
1683-P
Differential Response of Mitochondrial Enzymes to Obesity and
Excessive Dietary Fat Intake
ELIZAVETA V. MENCHIKOVA, WAN HUANG, FREDERICO G.S. TOLEDO, ROBERT
M. O’DOHERTY, BRET H. GOODPASTER, VLADIMIR B. RITOV, Pittsburgh, PA
The current study was undertaken to compare the effect of obesity or
excessive fat intake on specifi c activity (per mitochondria mass) of electrontransport
chain (NADH-oxidase) and TCA cycle (citrate synthase (CS) that
provides entrance of acetyls into TCA cycle) enzymes in human skeletal muscle
and rat liver. Tissue cardiolipin (CL) content was measured as independent
non-enzymatic marker of mitochondrial mass. We compared CL, NADHoxidase
and CS activity in skeletal muscle biopsies from sedentary lean
insulin sensitive (L, n=9, age 47±2, BMI 24±1) and sedentary obese insulin
resistant (Ob, n=15, age 42±3, BMI 35±1) subjects. There is no difference
in CL content in skeletal muscle from L and Ob (74±9 and 76±6 μg/mU CK,
respectively). The activity of NADH-oxidase was reduced signifi cantly in Ob
in comparison with L (5.63±1.59 and 2.45±0.23 U/mg CL (P=0.02) for L and Ob
subjects, respectively). However, the citrate synthase activity is signifi cantly
higher in obesity in comparison with lean group (35.8±3.4 and 54.5±5.3 U/mg
CL (P=0.02) for L and Ob, respectively).
Analysis of liver mitochondria was performed on a rodent high-fat feeding
model. Five weeks of high–fat feeding in rats (n=4) induces insulin resistance,
decreases specifi c NADH-oxidase activity (1.470±0.53 and 0.997±0.08 U/
mg CL for control (C) and high fat-fed (HF) rats, respectively), signifi cantly
increases citrate synthase activity (19.7±2.1 and 27.4±1.4 U/mg CL (P=0.023)
for C and HF rats, respectively) and slightly decreases liver cardiolipin
content. We hypothesize that excessive dietary fat intake induces activation
of CS (by induction of protein synthesis or by post-translational modifi cation
in liver and skeletal muscle) to utilize excessive acetyl-CoA produced in
beta-oxidation pathway.
These data highlight that mitochondrial TCA cycle and electron transport
chain enzymes respond differently to energy excess. Further investigation is
needed to better understand the respective roles of specifi c mitochondrial
function in obesity and insulin resistance. ADA-Funded Research
1684-P
Effect of Ecdysterone on Hepatic AMP Activated Protein Kinase in
Mice Fed with a High-Fat Diet
ZHONG Q. WANG, YONGMEI YU, XIAN H. ZHANG, DAVID RIBNICKY, WILLIAM T.
CEFALU, Baton Rouge, LA, New Brunswick, NJ
Chronic nutrient overload leads to obesity and metabolic disorders,
including insulin resistance and type 2 diabetes. Ecdysterone (Ecdy),
specifi cally20-hydroxyecdysone, is a steroid hormone from plants). Our
previous study showed that Ecdy may have anti-obesity and anti-diabetic
effects, but its molecular mechanisms remain largely unknown. It is well
documented AMP activated protein kinase (AMPK) plays a key role in glucose
metabolism. In order to evaluate the effect of Ecdy on AMPK signaling, we
examined hepatic AMPK pathway proteins in mice fed a low-fat diet (control)
or high-fat diet (HFD) with or without low dose (25 mg/kg body weight, Ecdy
L) or high-dose (50 mg/kg, Ecdy H) of Ecdy for 12 weeks. Body weight, fasting
glucose and insulin concentrations were measured as well. At study end,
no differences in body weight, food intake or energy expenditure were
observed between HFD groups with or without Ecdy L, but the body weight
was signifi cantly lower in Ecdy H group relative to the HFD group (P