Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids.
BACKGROUND
The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]).


RESULTS
Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05).


CONCLUSIONS
These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism.
Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
Jaime L
JL
Lecker
Nirupa R
NR
Matthan
Jeffrey T
JT
Billheimer
Daniel J
DJ
Rader
Alice H
AH
Lichtenstein
D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000009:adverse effects; D006224:Cricetinae; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000627:therapeutic use*; D005395:Fish Oils / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006706:Homeostasis; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012450:Safflower Oil / Q000627:therapeutic use; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
D001053:Apolipoproteins; D002791:Cholesterol, Dietary; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D008074:Lipoproteins; D012333:RNA, Messenger; D011973:Receptors, LDL; D051780:Sterol Regulatory Element Binding Protein 1; D012450:Safflower Oil; D002784:Cholesterol; D000101:Acetyl-CoA C-Acetyltransferase