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Fish oil minimises feed intake and improves insulin sensitivity in Zucker fa/fa rats

Published online by Cambridge University Press:  25 October 2023

Charlotte Corporeau
Affiliation:
Department of Nutritional Sciences, Hospital University, Faculty of Medicine, University of Brest, Plouzané, France Present address: Ifremer, University of Brest, CNRS, IRD, LEMAR, F-29280 Plouzané, France
Christelle Le Foll
Affiliation:
Department of Nutritional Sciences, Hospital University, Faculty of Medicine, University of Brest, Plouzané, France Present address: Institute of Veterinary Physiology, University of Zurich, CH-8057, Zurich, Switzerland
Céline Cruciani-Guglielmacci
Affiliation:
Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France
Hervé Le Stunff
Affiliation:
Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France Present address: Institut des Neurosciences Paris-Saclay-Université Paris-Saclay-CNRS UMR 9197, Gif-sur-Yvette, France
Gilles Mithieux
Affiliation:
Inserm, U855, Lyon, F-69008, France University Lyon 1, Villeurbanne, F-69622, France University of Lyon, Lyon, F-69008, France
Christophe Magnan
Affiliation:
Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France
Jacques Delarue*
Affiliation:
Department of Nutritional Sciences, ER7479 SPURBO, Hospital University, Faculty of Medicine University of Brest, Plouzane, France
*
*Corresponding author: Jacques Delarue, email jacques.delarue@univ-brest.fr

Abstract

Long-chain n-3 PUFA (LC n-3 PUFA) prevent, in rodents, insulin resistance (IR) induced by a high-fat and/or fructose diet but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZOFO), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZOCO). Male lean Zucker (ZL) rats fed either FO (ZLFO) or CO (ZLCO) diet were used as controls. FO was a marine-derived TAG oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZOFO only. Liver insulin sensitivity (euglycaemic–hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZOFO rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZOFO and ZOCO. Hypothalamic ceramides levels were lower in ZOFO than in ZOCO. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

Type
Research Article
Copyright
© University of Brest, 2023. Published by Cambridge University Press on behalf of The Nutrition Society

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References

Delarue, J (2020) Are marine n-3 fatty acids protective towards insulin resistance? From cell to human. Proc Nutr Soc 6, 111.CrossRefGoogle Scholar
Delpino, FM, Figueiredo, LM, da Silva, BGC, et al. (2021) n-3 supplementation and diabetes: A systematic review and meta-analysis. Crit Rev Food Sci Nutr 62, 114.Google Scholar
Storlien, LH, Kraegen, EW, Chisholm, DJ, et al. (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237, 885888.CrossRefGoogle ScholarPubMed
Taouis, M, Dagou, C, Ster, C, et al. (2002) n-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle. Am J Physiol Endocrinol Metab 282, E664E671.CrossRefGoogle ScholarPubMed
Podolin, DA, Gayles, EC, Wei, Y, et al. (1998) Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in rats. Am J Physiol 274, R840R848.Google Scholar
Guriec, N, Le Foll, C & Delarue, J (2023) Long-chain n-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner. Br J Nutr 130, 11211136.CrossRefGoogle Scholar
Le Foll, C, Corporeau, C, Le Guen, V, et al. (2007) Long-chain n-3 polyunsaturated fatty acids dissociate phosphorylation of Akt from phosphatidylinositol 3'-kinase activity in rats. Am J Physiol Endocrinol Metab 292, E1223E1230.CrossRefGoogle ScholarPubMed
Delarue, J, Allain-Jeannic, G, Guillerm, S, et al. (2016) Interaction of low dose of fish oil and glucocorticoids on insulin sensitivity and lipolysis in healthy humans: a randomized controlled study. Mol Nutr Food Res 60, 886896.CrossRefGoogle ScholarPubMed
Zucker, LM & Zucker, TF (1961) Fatty, a new mutation in the rat. J Heredity 52, Suppl. 6, 275278.CrossRefGoogle Scholar
Takaya, K, Ogawa, Y, Isse, N, et al. (1996) Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats. Biochem Biophys Res Commun 225, 7583.CrossRefGoogle ScholarPubMed
Wang, B, Chandrasekera, PC & Pippin, JJ (2014) Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Curr Diabetes Rev 10, 131145.CrossRefGoogle ScholarPubMed
Dufresne, J, Hoang, T, Ajambo, J, et al. (2017) Freeze-dried plasma proteins are stable at room temperature for at least 1 year. Clin Proteomics 14, 35.CrossRefGoogle ScholarPubMed
Nkuna, DX, Khoza, SP, George, JA, et al. (2023) The stability of C-peptide and insulin in plasma and serum samples under different storage conditions. Clin Chem Lab Med 61, 21502158.CrossRefGoogle ScholarPubMed
Holm, AM, Johansen, PB, Ahnfelt-Rønne, I, et al. (2004) Adipogenic and orexigenic effects of the ghrelin-receptor ligand tabimorelin are diminished in leptin-signalling-deficient ZDF rats. Eur J Endocrinol 150, 893904.CrossRefGoogle ScholarPubMed
Gilbert, M, Magnan, C, Turban, S, et al. (2003) Leptin receptor- deficient obese Zucker rats reduce their food intake in response to a systemic supply of calories from glucose. Diabetes 52, 277282.CrossRefGoogle ScholarPubMed
Lee, KH & Kim, NH (2019) Differential expression of adipocyte-related molecules in the distal epididymal fat of mouse during postnatal period. Dev Reprod 23, 213221.CrossRefGoogle ScholarPubMed
Zhao, J, Feng, Y, Rao, Z, et al. (2023) Exercise combined with heat treatment improves insulin resistance in diet-induced obese rats. J Therm Biol 116, 103651.CrossRefGoogle ScholarPubMed
Marsollier, N, Kassis, N, Mezghenna, K, et al. (2009) Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. PLoS One 4, e6649.CrossRefGoogle ScholarPubMed
Joly-Amado, A, Soty, M, Philippe, E, et al. (2022) Portal glucose infusion, afferent nerve fibers, and glucose and insulin tolerance of insulin-resistant rats. J Nutr 152, 18621871.CrossRefGoogle ScholarPubMed
Kim, JK, Gimeno, RE, Higashimori, T, et al. (2004) Inactivation of fatty acid transport protein 1 prevents fat- induced insulin resistance in skeletal muscle. J Clin Invest 113, 756763.CrossRefGoogle ScholarPubMed
Rajas, F, Bruni, N, Montano, S, et al. (1999) The glucose-6 phosphatase gene is expressed in human and rat small intestine: regulation of expression in fasted and diabetic rats. Gastroenterology 117, 132139.CrossRefGoogle ScholarPubMed
Mutel, E, Gautier-Stein, A, Abdul-Wahed, A, et al. (2011) Control of blood glucose in the absence of hepatic glucose production during prolonged fasting in mice: induction of renal and intestinal gluconeogenesis by glucagon. Diabetes 60, 31213131.CrossRefGoogle ScholarPubMed
Rajas, F, Croset, M, Zitoun, C, et al. (2000) Induction of PEPCK gene expression in insulinopenia in rat small intestine. Diabetes 49, 11651168.CrossRefGoogle ScholarPubMed
Jomain-Baum, M & Schramm, VL (1978) Kinetic mechanism of phosphoenolpyruvate carboxykinase (GTP) from rat liver cytosol. Product inhibition, isotope exchange at equilibrium, and partial reactions. J Biol Chem 253, 36483659.CrossRefGoogle ScholarPubMed
Lowry, OH, Rosebrough, NJ, Farr, AL, et al. (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193, 265275.CrossRefGoogle ScholarPubMed
Bligh, EG & Dyer, WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37, 911917.CrossRefGoogle ScholarPubMed
Berge, JP, Debiton, E, Dumay, J, et al. (2002) In vitro anti- inflammatory and anti-proliferative activity of sulfolipids from the red alga Porphyridium cruentum. J Agric Food Chem 50, 62276232.CrossRefGoogle ScholarPubMed
Escalante-Alcalde, D, Hernandez, L, Le Stunff, H, et al. (2003) The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning. Development 130, 46234637.CrossRefGoogle ScholarPubMed
Le Stunff, H, Galve-Roperh, I, Peterson, C, et al. (2002) Sphingosine- 1-phosphate phosphohydrolase in regulation of sphingolipid metabolism and apoptosis. J Cell Biol 158, 10391049.CrossRefGoogle ScholarPubMed
DeFronzo, RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37, 667687.CrossRefGoogle ScholarPubMed
Neschen, S, Morino, K, Dong, J, et al. (2007) n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator- activated receptor-α-dependent manner. Diabetes 56, 10341041.CrossRefGoogle Scholar
Daniele, N, Bordet, JC & Mithieux, G (1997) Unsaturated fatty acids associated with glycogen may inhibit glucose-6 phosphatase in rat liver. J Nutr 127, 22892292.CrossRefGoogle ScholarPubMed
Daniele, N, Rajas, F, Payrastre, B, et al. (1999) Phosphatidylinositol 3-kinase translocates onto liver endoplasmic reticulum and may account for the inhibition of glucose-6-phosphatase during refeeding. J Biol Chem 274, 35973601.CrossRefGoogle ScholarPubMed
Rajas, F, Gautier, A, Bady, I, et al. (2002) Polyunsaturated fatty acyl coenzyme A suppress the glucose-6-phosphatase promoter activity by modulating the DNA binding of hepatocyte nuclear factor 4 alpha. J Biol Chem 277, 1573615744.CrossRefGoogle ScholarPubMed
Mithieux, G, Daniele, N, Payrastre, B, et al. (1998) Liver microsomal glucose-6- phosphatase is competitively inhibited by the lipid products of phosphatidylinositol 3-kinase. J Biol Chem 273, 1719.CrossRefGoogle ScholarPubMed
Minassian, C, Tarpin, S & Mithieux, G (1998) Role of glucose-6 phosphatase, glucokinase, and glucose-6 phosphate in liver insulin resistance and its correction by metformin. Biochem Pharmacol 55, 12131219.CrossRefGoogle ScholarPubMed
Mithieux, G, Guignot, L, Bordet, JC, et al. (2002) Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high- fat diet. Diabetes 51, 139143.CrossRefGoogle ScholarPubMed
Romanatto, T, Fiamoncini, J, Wang, B, et al. (2014) Elevated tissue n-3 fatty acid status prevents age-related glucose intolerance in fat-1 transgenic mice. Biochim Biophys Acta 1842, 186191.CrossRefGoogle ScholarPubMed
Delarue, J & Magnan, C (2007) Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care 10, 142148.CrossRefGoogle ScholarPubMed
Neschen, S, Moore, I, Regittnig, W, et al. (2002) Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab 282, E395E401.CrossRefGoogle ScholarPubMed
Pavlisova, J, Bardova, K, Stankova, B, et al. (2016) Corn oil v. lard: Metabolic effects of n-3 fatty acids in mice fed obesogenic diets with different fatty acid composition. Biochimie 124, 150162.CrossRefGoogle Scholar
Fougerat, A, Montagner, A, Loiseau, N, et al. (2020) Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease. Cells 9, 1638.CrossRefGoogle ScholarPubMed
Jump, DB, Tripathy, S & Depner, CM (2013) Fatty acid-regulated transcription factors in the liver. Annu Rev Nutr 33, 249269.CrossRefGoogle ScholarPubMed
Xu, J, Nakamura, MT, Cho, HP, et al. (1999) Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats. J Biol Chem 274, 2357723583.CrossRefGoogle ScholarPubMed
Dentin, R, Benhamed, F, Pégorier, JP, et al. (2005) Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation. J Clin Invest 115, 28432854.CrossRefGoogle ScholarPubMed
Delarue, J & Lallès, JP (2016) Nonalcoholic fatty liver disease: roles of the gut and the liver and metabolic modulation by some dietary factors and especially long-chain n-3 PUFA. Mol Nutr Food Res 6, 147159.CrossRefGoogle Scholar
Yang, Q, Wang, S, Ji, Y, et al. (2017) Dietary intake of n-3 PUFAs modifies the absorption, distribution and bioavailability of fatty acids in the mouse gastrointestinal tract. Lipids Health Dis 16, 10.CrossRefGoogle ScholarPubMed
Cintra, DE, Ropelle, ER, Moraes, JC, et al. (2012) Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. PLoS One 7, e30571.CrossRefGoogle ScholarPubMed
Schwinkendorf, DR, Tsatsos, NG, Gosnell, BA, et al. (2011) Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism. Int J Obes 35, 336344.CrossRefGoogle ScholarPubMed
Cao, W, Liu, F, Li, RW, et al. (2022) Triacylglycerol rich in docosahexaenoic acid regulated appetite via the mediation of leptin and intestinal epithelial functions in high-fat, high-sugar diet-fed mice. J Nutr Biochem 99, 108856.CrossRefGoogle Scholar
Huang, XF, Xin, X, McLennan, P, et al. (2044) Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression. Diabetes Obes Metab 6, 3544.CrossRefGoogle Scholar
Viggiano, E, Mollica, MP, Lionetti, L, et al. (2016) Effects of an high-fat diet enriched in lard or in fish oil on the hypothalamic amp-activated protein kinase and inflammatory mediators. Front Cell Neurosci 10, 150.CrossRefGoogle ScholarPubMed
Fang, X, Ge, K, Song, C, et al. (2018) Effects of n-3PUFAs on autophagy and inflammation of hypothalamus and body weight in mice. Biochem Biophys Res Commun 501, 927932.CrossRefGoogle ScholarPubMed
Pascoal, LB, Bombassaro, B, Ramalho, AF, et al. (2017) Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity. J Neuroinflammation 14, 5.CrossRefGoogle ScholarPubMed
Wellhauser, L & Belsham, DD (2014) Activation of the n-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons J Neuroinflammation 11, 60.CrossRefGoogle ScholarPubMed
Jais, A & Brüning, JC (2017) Hypothalamic inflammation in obesity and metabolic disease. J Clin Invest 127 Suppl. 1, 2432.CrossRefGoogle ScholarPubMed
Harden, CJ, Dible, VA, Russell, JM, et al. (2014) Long-chain polyunsaturated fatty acid supplementation had no effect on body weight but reduced energy intake in overweight and obese women. Nutr Res 34, 1724.CrossRefGoogle ScholarPubMed
Payahoo, L, Ostadrahimi, A, Farrin, N, et al. (2018) Effects of n-3 polyunsaturated fatty acid supplementation on serum leptin levels, appetite sensations, and intake of energy and macronutrients in obese people: a randomized clinical trial. J Diet Suppl 15, 596605.CrossRefGoogle ScholarPubMed
Parra, D, Ramel, A, Bandarra, N, et al. (2008) A diet rich in long chain n-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss. Appetite 51, 676680.CrossRefGoogle Scholar
Campana, M, Bellini, L, Rouch, C, et al. (2018) Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats. Mol Metab 8, 2336.CrossRefGoogle ScholarPubMed
Jayasinghe, SU, Tankeu, AT & Amati, F (2019) Reassessing the role of diacylglycerols in insulin resistance. Trends Endocrinol Metab 30, 618635.CrossRefGoogle ScholarPubMed
Sokolowska, E & Blachnio-Zabielska, A (2019) The role of ceramides in insulin resistance. Front Endocrinol 10, 577.CrossRefGoogle ScholarPubMed
Bandet, CL, Tan-Chen, S, Bourron, O, et al. (2019) Sphingolipid metabolism: new insight into ceramide-induced lipotoxicity in muscle cells. Int J Mol Sci 20, 479.CrossRefGoogle ScholarPubMed
Petersen, MC & Shulman, GI (2018) Mechanisms of insulin action and insulin resistance. Physiol Rev 98, 21332223.CrossRefGoogle ScholarPubMed
Huang, XF, Xin, X, McLennan, P, et al. (2004) Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression. Diabetes Obes Metab 6, 3544.CrossRefGoogle ScholarPubMed
Jang, H & Park, K (2020) n-3 and n-6 polyunsaturated fatty acids and metabolic syndrome: a systematic review and meta-analysis. Clin Nutr 39, 765773.CrossRefGoogle Scholar
Lee, JS, Pinnamaneni, SK, Eo, SJ, et al. (1985) Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol 100, 14671474.CrossRefGoogle Scholar
Brady, LM, Lovegrove, SS, Lesauvage, SV, et al. (2004) Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians. Am J Clin Nutr 79, 983991.CrossRefGoogle ScholarPubMed
Wu, JHY, Marklund, M, Imamura, F, et al. (2017) n-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. Lancet Diabetes Endocrinol 5, 965974.CrossRefGoogle ScholarPubMed
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