2011 ADA Posters 1261-2041.indd - Diabetes

1839-P
Omega-3 Fatty Acids Protect Against Glucose Intolerance and
Attenuate Ceramide Accumulation with High Fat Diet
IAN LANZA, AGNIESZKA ZABIELSKI, PIOTR ZABIELSKI, DANIEL JAKAITIS,
BUSHRA ALI, K. SREEKUMARAN NAIR, Rochester, MN
Lipotoxicity is implicated as a cause of insulin resistance. Accumulation
of lipid metabolites (e.g., ceramides) may interfere with insulin signaling in
muscle. Dietary omega-3 fatty acids (n3PUFA) are reported to protect against
insulin resistance with high-fat diets. We determined the impact of n3PUFA
on the content and composition of lipid metabolites in skeletal muscle. Mice
were fed for 10wks with normal fat diet (NF, 10% fat), high fat diet (HF, 60%
fat), or high fat diet + fi sh oil (HF+N3, 60% fat with 3.4% kcals from n3PUFA).
Oral glucose tolerance tests (OGTT) were performed at baseline and 10wks.
Muscle tissue was homogenized and separated into sarcoplasmic, myofi brillar,
and mitochondrial fractions. Ceramides and long chain acyl coA (LCACoA)
were measured by mass spectrometry using internal standards for individual
species. OGTT revealed signifi cant reductions in glucose tolerance in HF
but not HF+N3 or NFD. Total ceramide was increased in HF (15.69±0.41 ng/
mg tissue) and HF+N3 (14.38±0.16) compared to NFD (13.05±0.43). Closer
examination of individual ceramide species revealed that n3-PUFAs completely
prevented HF-induced increases in medium chain saturated (C18) ceramides
(NF: 7.38±0.31, HF: 9.41±0.27, HF+N3: 8.08±0.17 ng/mg tissue), but signifi cantly
increased levels of long chain monounsaturated (C24:1) ceramides ceramides
(NF: 2.74±0.06, HF: 2.45±0.06, HF+N3: 2.76±0.04 ng/mg tissue). Regression
analyses revealed that C18 ceramide content is a strong predictor (R 2 =0.57,
P