Abstract
The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated
(fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma
glucose and lipid controls in a dietary insulin resistance model using sucrose-fed
rats. The underlying cellular and molecular mechanisms were also determined in the
muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized
for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF),
olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group
(C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks
on the diet, body weight was comparable in the four groups. The sucrose-fed rats were
hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish
oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia,
but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in
adipocytes increased after feeding with fish oil (p < 0.005). These modifications
were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes.
In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could
not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein
levels. We therefore conclude that the presence of fish oil, in contrast to olive
oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet,
and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels.
Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend
on insulin stimulation and/or duration of dietary interventions.
Key words
Fish Oil - Olive Oil - Adipocytes - Muscle - Glucose Transport - Dietary Insulin Resistance
References
1
Bang H O, Dyeberg J, Nielsen A B.
Plasma lipid and lipoprotein pattern in greenland west coast Eskimos.
Lancet.
1971;
1
143-1145
2
Keys A, Menotti A, Aravanis C.
The seven countries study: 2289 deaths in 15 years.
Prev Med.
1984;
13
141-154
3
Kasime E, Stern B, Khilnani S, Lin P M, Baciorowski S, Jen K L.
Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure
in type 2 diabetic patients.
J Clin Endoc Met.
1988;
67
1-5
4
Glauber H, Wallace P, Griver K, Brechtel G.
Adverse metabolic effect of omega-3 fatty acids in non insulin dependent diabetes
mellitus.
Ann Intern Med.
1988;
108
663-668
5
Friday K, Childs M, Tsunehara C, Fugimoto W, Bierman E.
Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid supplementation
in type 2 diabetes.
Diabetes Care.
1989;
12, 4
276-281
6
Garg A.
Treatment of diabetic dyslipidemia.
Am J Cardiol.
1998;
81
47B-51B
7
Campbell L V, Marmot P E, Dyer J A, Borckman M, Storlien L H.
The high monounsaturated fat diet as a practical alternative for NIDDM.
Diabetes care.
1994;
17 (3)
177-182
8
Garg A, Bantle J P, Henry R, Coulstom A M, Griver K A, Raatz S K, Brinkley L, Chen I,
Grundy S M, Huet B A, Reaven G M.
Effects of varying carbohydrate content of diet in patients with non-insulin-dependant
diabetes mellitus.
JAMA.
1994;
271
1421-1428
9
Storlien L H, Kraegen E W, Chisholm D J, Ford G L, Bruce D G, Pascoe W S.
Fish oil prevents insulin resistance induced by high fat feeding.
Science.
1987;
237
885-888
10
Luo J, Rizkalla S W, Boillot J, Alamowitch C, Chaib H, Bruzzo F, Desplanque N, Dalix A M,
Durand G, Slama G.
Dietary (n-3) polyunsaturated fatty acids improve adipocyte insulin action and glucose
metabolism in insulin-resistant rats: relation to membrane fatty acids.
J Nutr.
1996;
126 (8)
1951-1958
11
Kim J, Nolte L, Hansen P, Han D, Freguson K, Thompson P, Holloszy J.
High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass.
Am J Physiol.
2000;
279
R2057-R2065
12
Rodbell M.
Effects of hormones on glucose metabolism and lipolysis.
J Biol Chem.
1964;
239
375-380
13
Lavau M, Susini C, Knittle J, Blanchet-Hirst S, Greenwood M R.
A reliable photomicrographic method for determining fat cell size and number: application
for dietary obesity.
Proc Soc Exp Biol Med.
1977;
156
251-256
14
Goldrick R B.
Morphological changes in adipocyte timing of fat deposition and mobilization.
Am J Physiol.
1967;
212
777-782
15
Dole V P, Meinertz H.
Microdetermination of long-chain fatty acids in plasma and tissues.
J Biol Chem.
1960;
235
2595-2599
16
Guerre-Millo M, Lavau M, Horne J S, Wardzala L J.
Proposed mechanism for increased insulin-mediated glucose transport in adipose cells
from young, obese Zucker rats. Large intracellular pool of glucose transporters.
J Biol Chem.
1985;
260
2197-2201
17
Joost H G, Weber T M, Cushman S W.
Qualitative and quantitative comparison of glucose transport activity and glucose
transporter concentration in plasma membranes from basal and insulin-stimulated rat
adipose cells.
Biochem J.
1988;
249
155-161
18
Chomczynski P, Sacchi N.
Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform
extraction.
Ann Biochem.
1987;
162
156-159
19
Janke J, Engeli S, Gorzelniak K, Sharma A M.
Extraction of total RNA from adipocytes.
Horm Metab Res.
2001;
33
213-215
20
Charron J M.
A glucose transport protein expressed predominately in insulin-responsive tissues.
PNAS USA.
1989;
86
2535-2539
21
Gorzelniak K, Janke J, Engeli S, Sharma A M.
Validation of endogenous controls for gene expression studies in human adipocytes
and preadipocytes.
Horm Metab Res.
2001;
33
625-627
22 Breil V, Rouault C, Rizkalla S W, Broca C, Taouis M, Petit P, Reach G. 4-Hydroxyisoleucine
improves insulin sensitivity in insulin resistant rats. Effect of 4-hydroxyisoleucine
on insulin sensitivity. Diabetes (submitted in 2002)
23
Breil V, Rouault C, Rizkalla S W, Broca C, Taouis M, Petit P, Reach G.
Effect of 4-hydroxyisoleucine on insulin sensitivity in insulin resistant rats.
Diabetologia.
2001;
44 Suppl. 1
A79
24
Storlien L H, Kraegen E W, Jenkins A B, Chisholm D J.
Effects of sucrose vs. starch diets on in vivo insulin action, thermogenesis, and obesity in rats.
Am J Clin Nutr.
1988;
47
420-427
25
D’Alessandro M E, Chicco A, Karabatas L, Lombardo Y B.
Role of skeletal muscle on impaired insulin sensitivity in rats fed a sucrose-rich
diet: Effect of moderate levels of dietary fish oil.
J Nutr Biochem.
2000;
11
273-280
26
Kim J, Notle L, Hansen P, Han D, Kawanaka K, Holloszy J.
Insulin resistance of muscle glucose transport in male and female rats fed high-sucrose
diet.
Am J Physiol.
1999;
276
R665-R672
27
Vrana A, Kazdova L.
Effects of dietary sucrose and fructose on carbohydrate and lipid metabolism.
Animal studies Prog Biochem Pharmacol.
1986;
21
59-73
28
Podolin D A, Gayles E C, Wei Y, Thresher J S, Pagliassotti M J.
Menhaden oil prevents but not reverse sucrose-induced insulin resistance in rats.
Am J Physiol.
1998;
274
R840-R848
29
Riccardi G, Rivellese A A.
Dietary treatment of the metabolic syndrome - the optimal diet.
Br J Nutr.
2000;
83, 1
S143-S148
30
Zisman A, Peroni O D, Abel E D, Michael M D, Mauvais-Jarvis F, Lowell-Wojtaszewski J F,
Hirshman M F, Virkamaki A, Goodyear L J, Khan C R, Khan B B.
Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin
resistance and glucose intolerance.
Nat Med.
2000;
6
924-928
31
Giron M, Salto R, Hortelano P, Periago J, Vargas A, Suarez M.
Increased diaphragm expression of GLUT4 in control and streptozotocin-diabetic rats
by fish oil-supplemented diets.
Lipids.
1999;
34
801-807
32
Klimes I, Sebokova E, Minchenko A, Maassen T, Moss R, Mitkova A, Wiersma M, Bohov P.
Glut-4 gene expression and Glut-4 protein levels in muscle of high sucrose-fed rats:
effects of dietary fish oil.
J Nutr Biochem.
1994;
5
389-396
33
Sebokova E, Klimes I, Moss R, Mitkova A, Wiersma M, Bohov P.
Decreased glucose transporter protein (GLUT4) in skeletal muscle of hypertriglyceridaemic
insulin-resistant rat.
Physiol Res.
1995;
44
87-92
34
Mori Y, Murakawa Y, Katoh S, Hata S, Yokoyama J, Tajima N, Ikeda Y, Nobukata H, Ishikawa T,
Shibutani Y.
Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance
in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent
diabetes mellitus.
Metabolism.
1997;
46
1458-1464
35
Kainulainen H, Komulainen J, Joost H G, Vihko V.
Dissociation of the effects of training on oxidative metabolism, glucose utilisation
and GLUT-4 levels in skeletal muscle of streptozotocin-diabetic rats.
European Journal of Physiology.
1994;
427
444-449
36
Kern M, Loomis T A, Tapscott E B, Dohm G L.
Increased muscle glucose uptake in response to chronic glyburide treatment is not
related to changes in glucose transporter (GLUT-4) protein.
Int J Biochem.
1993;
25
1257-1261
37
Kahn B B, Pederson O.
Suppression of GLUT-4 expression in skeletal muscle of rats that are obese from high
fat feeding but not from high carbohydrate feeding or genetic obesity.
Endocrinology.
1993;
132
13-22
38
Ezaki O, Tsuji E, Momomura K, Kasuga M, Itakura H.
Effects of fish and safflower oil feeding on subcellular glucose transporter distributions
in rat adipocytes.
Am J Physiol.
1992;
263
E94-E101
Dr. S. W. Rizkalla
Service de diabétologie · INSERM U341
Hôpital Hôtel-Dieu
1 place du parvis Notre-Dame · 75 181 Paris, Cedex 04 · France ·
Phone: + 33 (1) 42 34 83 95
Email: salwa.rizkalla@htd.ap-hop-paris.fr