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DOI: 10.1055/s-0030-1247544
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Development of Glucose Intolerance in Wistar Rats Fed Low and Moderate Fat Diets Differing in Fatty Acid Profile
Publikationsverlauf
received 02.01.2009
first decision 25.11.2009
accepted 13.01.2010
Publikationsdatum:
25. Februar 2010 (online)

Abstract
Background/Aims: Both dietary fat content and fatty acid composition play a role in the development of glucose intolerance and insulin resistance. In this study we investigated the effect of moderate increases in dietary fat (10–30% of fat as total calories) and associated differences in fatty acid content, on the development of metabolic perturbations in the Wistar rat.
Methods: Eighteen normal male Wistar rats were randomly divided into 3 groups (n=6 each) at weaning, and fed different diets for 10 months: D10–10% fat as energy; D20–20% fat as energy and D30–30% fat as energy ad libitum.
Results: Compared with D10, rats fed D20 and D30 exhibited increased body weight from as early as 1 month of the study (p<0.01). None of the diets resulted in hyperglycemia, but glucose intolerance developed as early as 1 month in the D20 and D30 groups (p<0.01) following intravenous glucose tolerance test. Over time, the glucose stimulated insulin secretion rate (GSIS) became more blunted in the D20 and D30 groups, but by 10 months the D20 group regained some insulin responsiveness. D30 showed very poor GSIS at 10 months indicating glucose intolerance. Plasma ω6 and ω3 fatty acid profiles mostly reflected the dietary content, but the ratio of ω6:ω3 in plasma deteriorated over time in D30, whereas that of D10 and D20 improved.
Conclusion: A moderate increase in dietary fat (20%), within the recommended nutritional range, and an unfavourable ω6:ω3 ratio resulted in glucose intolerance in this Wistar rat model, which was exacerbated with a further increase in dietary fat (30%).
Key words
fatty acids - insulin resistance - dietary fat
References
- 1
ADA
.
Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association.
Diabetes Care.
2007;
30
((1))
S48-S65
Reference Ris Wihthout Link
- 2
Ailhaud G, Massiera F, Weill P. et al .
Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive
adipose tissue development and relationship to obesity.
Prog Lipid Res.
2006;
45
((3))
203-236
Reference Ris Wihthout Link
- 3
Boden G.
Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.
Diabetes.
1997;
46
((1))
3-10
Reference Ris Wihthout Link
- 4
Bonora E, Bonadonna RC, Del Prato S. et al .
In vivo glucose metabolism in obese and type II diabetic subjects with or without
hypertension.
Diabetes.
1993;
42
((5))
764-772
Reference Ris Wihthout Link
- 5
Borkman M, Storlien LH, Pan DA. et al .
The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle
phospholipids.
N Engl J Med.
1993;
328
((4))
238-244
Reference Ris Wihthout Link
- 6
Buettner R, Newgard CB, Rhodes CJ. et al .
Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin
resistance by moderate hyperleptinemia.
Am J Physiol Endocrinol Metab.
2000;
278
((3))
E563-E569
Reference Ris Wihthout Link
- 7
Buettner R, Ottinger I, Scholmerich J. et al .
Preserved direct hepatic insulin action in rats with diet-induced hepatic steatosis.
Am J Physiol Endocrinol Metab.
2004;
286
((5))
E828-E833
Reference Ris Wihthout Link
- 8
Buettner R, Parhofer KG, Woenckhaus M. et al .
Defining high-fat-diet rat models: metabolic and molecular effects of different fat
types.
J Mol Endocrinol.
2006;
36
((3))
485-501
Reference Ris Wihthout Link
- 9
Carpentier A, Mittelman SD, Bergman RN. et al .
Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA
elevation.
Am J Physiol Endocrinol Metab.
1999a;
276
((6))
E1055-E1066
Reference Ris Wihthout Link
- 10
Carpentier A, Mittelman SD, Lamarche B. et al .
Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA
elevation.
Am J Physiol.
1999b;
276
((6 Pt 1))
E1055-E1066
Reference Ris Wihthout Link
- 11
Coll T, Eyre E, Rodriguez-Calvo R. et al .
Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal
muscle cells.
J Biol Chem.
2008;
283
((17))
11107-11116
Reference Ris Wihthout Link
- 12
Escriva F, Gavete ML, Fermin Y. et al .
Effect of age and moderate food restriction on insulin sensitivity in Wistar rats:
role of adiposity.
J Endocrinol.
2007;
194
((1))
131-141
Reference Ris Wihthout Link
- 13
Ferrannini E, Natali A, Bell P. et al .
Insulin resistance and hypersecretion in obesity. European Group for the Study of
Insulin Resistance (EGIR).
J Clin Invest.
1997;
100
((5))
1166-1173
Reference Ris Wihthout Link
- 14
Fukuchi S, Hamaguchi K, Seike M. et al .
Role of fatty acid composition in the development of metabolic disorders in sucrose-induced
obese rats.
Exp Biol Med (Maywood).
2004;
229
((6))
486-493
Reference Ris Wihthout Link
- 15
Gardner CD, Kiazand A, Alhassan S. et al .
Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related
risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a
randomized trial.
JAMA.
2007;
297
((9))
969-977
Reference Ris Wihthout Link
- 16
Griffin MD, Sanders TA, Davies IG. et al .
Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity,
lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45–70
y: the OPTILIP Study.
Am J Clin Nutr.
2006;
84
((6))
1290-1298
Reference Ris Wihthout Link
- 17
Guebre-Egziabher F, Rabasa-Lhoret R, Bonnet F. et al .
Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin
concentration and fatty acid oxidation in healthy subjects.
Eur J Clin Nutr.
2007;
Reference Ris Wihthout Link
- 18
Kahn SE.
The importance of the beta-cell in the pathogenesis of type 2 diabetes mellitus.
Am J Med.
2000;
108
(S 06)
S2-S8
Reference Ris Wihthout Link
- 19
Kahn SE.
The relative contributions of insulin resistance and beta-cell dysfunction to the
pathophysiology of Type 2 diabetes.
Diabetologia.
2003;
46
((1))
3-19
Reference Ris Wihthout Link
- 20
Khor GL.
Dietary fat quality: a nutritional epidemiologist's view.
Asia Pac J Clin Nutr.
2004;
13
S22
Reference Ris Wihthout Link
- 21
Lara-Castro C, Garvey WT.
Diet, insulin resistance, and obesity: zoning in on data for Atkins dieters living
in South Beach.
J Clin Endocrinol Metab.
2004;
89
((9))
4197-4205
Reference Ris Wihthout Link
- 22
Mason TM, Goh T, Tchipashvili V. et al .
Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory
response to glucose in vivo in rats.
Diabetes.
1999;
48
((3))
524-530
Reference Ris Wihthout Link
- 23
McAuley K, Mann J.
Thematic review series: patient-oriented research. Nutritional determinants of insulin
resistance.
J Lipid Res.
2006;
47
((8))
1668-1676
Reference Ris Wihthout Link
- 24
McGarry JD.
Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type
2 diabetes.
Diabetes.
2002;
51
((1))
7-18
Reference Ris Wihthout Link
- 25
Moussavi N, Gavino V, Receveur O.
Could the quality of dietary fat, and not just its quantity, be related to risk of
obesity?.
Obesity (Silver Spring).
2008;
16
((1))
7-15
Reference Ris Wihthout Link
- 26
Nigam A, Frasure-Smith N, Lesperance F. et al .
Relationship between n-3 and n-6 plasma fatty acid levels and insulin resistance in
coronary patients with and without metabolic syndrome.
Nutr Metab Cardiovasc Dis.
2008;
Reference Ris Wihthout Link
- 27
Oprescu AI, Bikopoulos G, Naassan A. et al .
Free fatty acid-induced reduction in glucose-stimulated insulin secretion: evidence
for a role of oxidative stress in vitro and in vivo.
Diabetes.
2007;
56
((12))
2927-2937
Reference Ris Wihthout Link
- 28
Pelikanova T, Kazdova L, Chvojkova S. et al .
Serum phospholipid fatty acid composition and insulin action in type 2 diabetic patients.
Metabolism.
2001;
50
((12))
1472-1478
Reference Ris Wihthout Link
- 29
Raatz SK, Bibus D, Thomas W. et al .
Total fat intake modifies plasma fatty acid composition in humans.
J Nutr.
2001;
131
((2))
231-234
Reference Ris Wihthout Link
- 30
Simopoulos AP.
Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional
implications for chronic diseases.
Biomed Pharmacother.
2006;
60
((9))
502-507
Reference Ris Wihthout Link
- 31
Simopoulos AP.
The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and
other chronic diseases.
Exp Biol Med (Maywood).
2008;
233
((6))
674-688
Reference Ris Wihthout Link
- 32
Stein DT, Esser V, Stevenson BE. et al .
Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in
the fasted rat.
J Clin Invest.
1996;
97
((12))
2728-2735
Reference Ris Wihthout Link
- 33
Storlien LH, Higgins JA, Thomas TC. et al .
Diet composition and insulin action in animal models.
Br J Nutr.
2000;
83
(S 01)
S85-S90
Reference Ris Wihthout Link
- 34
Storlien LH, Hulbert AJ, Else PL.
Polyunsaturated fatty acids, membrane function and metabolic diseases such as diabetes
and obesity.
Curr Opin Clin Nutr Metab Care.
1998;
1
((6))
559-563
Reference Ris Wihthout Link
- 35
Storlien LH, Jenkins AB, Chisholm DJ. et al .
Influence of dietary fat composition on development of insulin resistance in rats.
Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid.
Diabetes.
1991;
40
((2))
280-289
Reference Ris Wihthout Link
- 36
Storlien LH, Oakes ND, Pan DA. et al .
Syndromes of insulin resistance in the rat. Inducement by diet and amelioration with
benfluorex.
Diabetes.
1993;
42
((3))
457-462
Reference Ris Wihthout Link
- 37
Tichelaar HY, Spinnler Benade AJ, Daubitzer AK. et al .
An improved rapid thin-layer chromatographic-gas-liquid chromatographic procedure
for the determination of free fatty acids in plasma.
Clin Chim Acta.
1989;
183
((2))
207-215
Reference Ris Wihthout Link
- 38
Warnotte C, Gilon P, Nenquin M. et al .
Mechanisms of the stimulation of insulin release by saturated fatty acids. A study
of palmitate effects in mouse beta-cells.
Diabetes.
1994;
43
((5))
703-711
Reference Ris Wihthout Link
- 39
Wilson CR, Tran MK, Salazar KL. et al .
Western diet, but not high fat diet, causes derangements of fatty acid metabolism
and contractile dysfunction in the heart of Wistar rats.
Biochem J.
2007;
406
((3))
457-467
Reference Ris Wihthout Link
- 40
Winzell MS, Magnusson C, Ahren B.
Temporal and dietary fat content-dependent islet adaptation to high-fat feeding-induced
glucose intolerance in mice.
Metabolism.
2007;
56
((1))
122-128
Reference Ris Wihthout Link
- 41
Yaqoob P, Sherrington EJ, Jeffery NM. et al .
Comparison of the effects of a range of dietary lipids upon serum and tissue lipid
composition in the rat.
Int J Biochem Cell Biol.
1995;
27
((3))
297-310
Reference Ris Wihthout Link
Correspondence
Dr. A. Krygsman
Medical Research Council
Diabetes Discovery Platform
Francie van Zijl Drive
7505 Parow Valley
South Africa
eMail: akrygsman@sun.ac.za