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Horm Metab Res 2015; 47(03): 184-193
DOI: 10.1055/s-0034-1389991
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Improving Glucose Tolerance by Reducing Weight Gain in a Polygenic Obese Mouse Model: Use of a High Protein Diet

A. R. Blair
1   The University of Melbourne, Department of Medicine (Austin Health), Austin Hospital, Melbourne, Victoria, Australia
,
M. L. Strube
1   The University of Melbourne, Department of Medicine (Austin Health), Austin Hospital, Melbourne, Victoria, Australia
,
J. Proietto
1   The University of Melbourne, Department of Medicine (Austin Health), Austin Hospital, Melbourne, Victoria, Australia
,
S. Andrikopoulos
1   The University of Melbourne, Department of Medicine (Austin Health), Austin Hospital, Melbourne, Victoria, Australia
› Author Affiliations
Further Information

Publication History

received 12 May 2014

accepted 26 August 2014

Publication Date:
08 October 2014 (online)

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Abstract

Diets to decrease body weight have limited success in achieving and importantly maintaining this weight loss long-term. It has recently been suggested that energy intake can be regulated by the amount of protein ingested, termed the protein leverage hypothesis. In this study, we determined whether a high protein diet would be effective in achieving and maintaining weight loss in a genetically obese model, the New Zealand Obese (NZO) mouse. NZO and C57BL/6J (C57) control mice were fed a high protein or chow diet for 5 weeks from weaning (3 weeks of age). Body weight and food intake were determined. Mice on the same diet were bred to produce offspring that were fed either a chow or high protein diet. Body weight, food intake, and glucose tolerance were determined. Feeding NZO and C57 mice a high protein diet for 5 weeks resulted in reduced food intake and consequently energy intake and body weight gain compared with mice on a chow diet. NZO mice fed a high protein diet showed a significant improvement in glucose tolerance compared with their chow-fed counterparts, while no difference was seen in C57 mice fed chow or protein diet. The offspring of NZO mice that were fed a high protein diet during gestation and weaning were also lighter and displayed improved glucose tolerance compared with chow fed animals. We conclude that a high protein diet is a reasonable strategy to reduce body weight gain and improve glucose tolerance in the NZO mouse, a polygenic model of obesity.

Key words

New Zealand Obese mouse - high protein diet - weight gain - glucose tolerance
 

  • References

  • 1 Baker S, Jerums G, Proietto J. Effects and clinical potential of very-low-calorie diets (VLCDs) in type 2 diabetes. Diabetes Res Clin Pract 2009; 85: 235-242
    CrossrefPubMedGoogle Scholar
  • 2 Zraika S, Dunlop M, Proietto J, Andrikopoulos S. Effects of free fatty acids on insulin secretion in obesity. Obes Rev 2002; 3: 103-112
    CrossrefPubMedGoogle Scholar
  • 3 Kaiyala KJ, Schwartz MW. Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity pathogenesis. Diabetes 2011; 60: 17-23
    CrossrefPubMedGoogle Scholar
  • 4 Blakemore AI, Froguel P. Is obesity our genetic legacy?. J Clin Endocrinol Metab 2008; 93: S51-S56
    CrossrefPubMedGoogle Scholar
  • 5 Farooqi IS, O’Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 2008; 4: 569-577
    CrossrefPubMedGoogle Scholar
  • 6 Muller MJ, Bosy-Westphal A, Krawczak M. Genetic studies of common types of obesity: a critique of the current use of phenotypes. Obes Rev 2010; 11: 612-618
    CrossrefPubMedGoogle Scholar
  • 7 Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009; 41: 18-24
    CrossrefPubMedGoogle Scholar
  • 8 Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP, Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD, Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM, Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D, Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB, Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P, Kuokkanen M, Kuusisto J, Laitinen J, Lakatta EG, Luan J, Luben RN, Mangino M, McArdle WL, Meitinger T, Mulas A, Munroe PB, Narisu N, Ness AR, Northstone K, O’Rahilly S, Purmann C, Rees MG, Ridderstrale M, Ring SM, Rivadeneira F, Ruokonen A, Sandhu MS, Saramies J, Scott LJ, Scuteri A, Silander K, Sims MA, Song K, Stephens J, Stevens S, Stringham HM, Tung YC, Valle TT, Van Duijn CM, Vimaleswaran KS, Vollenweider P, Waeber G, Wallace C, Watanabe RM, Waterworth DM, Watkins N, Witteman JC, Zeggini E, Zhai G, Zillikens MC, Altshuler D, Caulfield MJ, Chanock SJ, Farooqi IS, Ferrucci L, Guralnik JM, Hattersley AT, Hu FB, Jarvelin MR, Laakso M, Mooser V, Ong KK, Ouwehand WH, Salomaa V, Samani NJ, Spector TD, Tuomi T, Tuomilehto J, Uda M, Uitterlinden AG, Wareham NJ, Deloukas P, Frayling TM, Groop LC, Hayes RB, Hunter DJ, Mohlke KL, Peltonen L, Schlessinger D, Strachan DP, Wichmann HE, McCarthy MI, Boehnke M, Barroso I, Abecasis GR, Hirschhorn JN. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41: 25-34
    CrossrefPubMedGoogle Scholar
  • 9 Grace C. A review of one-to-one dietetic obesity management in adults. J Hum Nutr Diet 2011; 24: 13-22
    CrossrefPubMedGoogle Scholar
  • 10 Grimm ER, Steinle NI. Genetics of eating behavior: established and emerging concepts. Nutr Rev 2011; 69: 52-60
    CrossrefPubMedGoogle Scholar
  • 11 Loveman E, Frampton GK, Shepherd J, Picot J, Cooper K, Bryant J, Welch K, Clegg A. The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: a systematic review. Health Technol Assess 2011; 15: 1-182
    Google Scholar
  • 12 Acheson KJ. Carbohydrate for weight and metabolic control: where do we stand?. Nutrition 2010; 26: 141-145
    CrossrefPubMedGoogle Scholar
  • 13 Astrup A. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008; 359: 2169-2172
    CrossrefPubMedGoogle Scholar
  • 14 Furlow EA, Anderson JW. A systematic review of targeted outcomes associated with a medically supervised commercial weight-loss program. J Am Diet Assoc 2009; 109: 1417-1421
    CrossrefPubMedGoogle Scholar
  • 15 Austin GL, Ogden LG, Hill JO. Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971–2006. Am J Clin Nutr 2011; 93: 836-843
    CrossrefPubMedGoogle Scholar
  • 16 Eckel RH, Kris-Etherton P, Lichtenstein AH, Wylie-Rosett J, Groom A, Stitzel KF, Yin-Piazza S. Americans’ awareness, knowledge, and behaviors regarding fats: 2006–2007. J Am Diet Assoc 2009; 109: 288-296
    CrossrefPubMedGoogle Scholar
  • 17 Haby MM, Markwick A, Peeters A, Shaw J, Vos T. Future predictions of body mass index and overweight prevalence in Australia, 2005–2025. Health Promot Int 2012; 27: 250-260
    CrossrefPubMedGoogle Scholar
  • 18 Simpson SJ, Raubenheimer D. Obesity: the protein leverage hypothesis. Obes Rev 2005; 6: 133-142
    CrossrefPubMedGoogle Scholar
  • 19 Sorensen A, Mayntz D, Raubenheimer D, Simpson SJ. Protein-leverage in mice: the geometry of macronutrient balancing and consequences for fat deposition. Obesity (Silver Spring) 2008; 16: 566-571
    CrossrefPubMedGoogle Scholar
  • 20 Brooks RC, Simpson SJ, Raubenheimer D. The price of protein: combining evolutionary and economic analysis to understand excessive energy consumption. Obes Rev 2010; 11: 887-894
    CrossrefPubMedGoogle Scholar
  • 21 Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Purnell JQ. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr 2005; 82: 41-48
    PubMedGoogle Scholar
  • 22 Paddon-Jones D, Westman E, Mattes RD, Wolfe RR, Astrup A, Westerterp-Plantenga M. Protein, weight management, and satiety. Am J Clin Nutr 2008; 87: 1558S-1561S
    PubMedGoogle Scholar
  • 23 Skov AR, Toubro S, Ronn B, Holm L, Astrup A. Randomized trial on protein vs. carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int J Obes Relat Metab Disord 1999; 23: 528-536
    CrossrefPubMedGoogle Scholar
  • 24 Due A, Toubro S, Skov AR, Astrup A. Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial. Int J Obes Relat Metab Disord 2004; 28: 1283-1290
    CrossrefPubMedGoogle Scholar
  • 25 Claessens M, van Baak MA, Monsheimer S, Saris WH. The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors. Int J Obes (Lond) 2009; 33: 296-304
    CrossrefPubMedGoogle Scholar
  • 26 Delbridge EA, Prendergast LA, Pritchard JE, Proietto J. One-year weight maintenance after significant weight loss in healthy overweight and obese subjects: does diet composition matter?. Am J Clin Nutr 2009; 90: 1203-1214
    CrossrefPubMedGoogle Scholar
  • 27 Andrikopoulos S, Rosella G, Gaskin E, Thorburn A, Kaczmarczyk S, Zajac JD, Proietto J. Impaired regulation of hepatic fructose-1,6-bisphosphatase in the New Zealand obese mouse model of NIDDM. Diabetes 1993; 42: 1731-1736
    CrossrefPubMedGoogle Scholar
  • 28 Andrikopoulos S, Proietto J. The biochemical basis of increased hepatic glucose production in a mouse model of type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1995; 38: 1389-1396
    CrossrefPubMedGoogle Scholar
  • 29 Veroni MC, Proietto J, Larkins RG. Evolution of insulin resistance in New Zealand obese mice. Diabetes 1991; 40: 1480-1487
    CrossrefPubMedGoogle Scholar
  • 30 Radavelli-Bagatini S, Blair AR, Proietto J, Spritzer PM, Andrikopoulos S. The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function. J Endocrinol 2011; 209: 307-315
    CrossrefPubMedGoogle Scholar
  • 31 Joost HG. The genetic basis of obesity and type 2 diabetes: lessons from the new zealand obese mouse, a polygenic model of the metabolic syndrome. Results Probl Cell Differ 2010; 52: 1-11
    PubMedGoogle Scholar
  • 32 Funkat A, Massa CM, Jovanovska V, Proietto J, Andrikopoulos S. Metabolic adaptations of three inbred strains of mice (C57BL/6, DBA/2, and 129T2) in response to a high-fat diet. J Nutr 2004; 134: 3264-3269
    PubMedGoogle Scholar
  • 33 Andrikopoulos S, Blair AR, Deluca N, Fam BC, Proietto J. Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab 2008; 295: E1323-E1332
    CrossrefPubMedGoogle Scholar
  • 34 Tamashiro KL, Wakayama T, Akutsu H, Yamazaki Y, Lachey JL, Wortman MD, Seeley RJ, D’Alessio DA, Woods SC, Yanagimachi R, Sakai RR. Cloned mice have an obese phenotype not transmitted to their offspring. Nat Med 2002; 8: 262-267
    CrossrefPubMedGoogle Scholar
  • 35 Soenen S, Westerterp-Plantenga MS. Proteins and satiety: implications for weight management. Curr Opin Clin Nutr Metab Care 2008; 11: 747-751
    CrossrefPubMedGoogle Scholar
  • 36 Potier M, Darcel N, Tome D. Protein, amino acids and the control of food intake. Curr Opin Clin Nutr Metab Care 2009; 12: 54-58
    CrossrefPubMedGoogle Scholar
  • 37 Veldhorst M, Smeets A, Soenen S, Hochstenbach-Waelen A, Hursel R, Diepvens K, Lejeune M, Luscombe-Marsh N, Westerterp-Plantenga M. Protein-induced satiety: effects and mechanisms of different proteins. Physiol Behav 2008; 94: 300-307
    CrossrefPubMedGoogle Scholar
  • 38 Veldhorst MA, Nieuwenhuizen AG, Hochstenbach-Waelen A, Westerterp KR, Engelen MP, Brummer RJ, Deutz NE, Westerterp-Plantenga MS. Effects of high and normal soyprotein breakfasts on satiety and subsequent energy intake, including amino acid and □satiety’ hormone responses. Eur J Nutr 2009; 48: 92-100
    CrossrefPubMedGoogle Scholar
  • 39 Bowen J, Noakes M, Clifton PM. Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. J Clin Endocrinol Metab 2006; 91: 2913-2919
    CrossrefPubMedGoogle Scholar
  • 40 Bowen J, Noakes M, Trenerry C, Clifton PM. Energy intake, ghrelin, and cholecystokinin after different carbohydrate and protein preloads in overweight men. J Clin Endocrinol Metab 2006; 91: 1477-1483
    CrossrefPubMedGoogle Scholar
  • 41 Faipoux R, Tome D, Gougis S, Darcel N, Fromentin G. Proteins activate satiety-related neuronal pathways in the brainstem and hypothalamus of rats. J Nutr 2008; 138: 1172-1178
    PubMedGoogle Scholar
  • 42 Larsen RN, Mann NJ, Maclean E, Shaw JE. The effect of high-protein, low-carbohydrate diets in the treatment of type 2 diabetes: a 12 month randomised controlled trial. Diabetologia 2011; 54: 731-740
    CrossrefPubMedGoogle Scholar
  • 43 Maurer AD, Chen Q, McPherson C, Reimer RA. Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood. J Physiol 2009; 587: 679-691
    CrossrefPubMedGoogle Scholar
  • 44 Maurer AD, Eller LK, Hallam MC, Taylor K, Reimer RA. Consumption of diets high in prebiotic fiber or protein during growth influences the response to a high fat and sucrose diet in adulthood in rats. Nutr Metab 2010; 7: 77
    CrossrefPubMedGoogle Scholar
  • 45 Maurer AD, Reimer RA. Maternal consumption of high-prebiotic fibre or -protein diets during pregnancy and lactation differentially influences satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring in rats. The British journal of nutrition 2011; 105: 329-338
    CrossrefPubMedGoogle Scholar
  • 46 Brehm BJ, D’Alessio DA. Benefits of high-protein weight loss diets: enough evidence for practice?. Curr Opin Endocrinol Diabetes Obes 2008; 15: 416-421
    CrossrefPubMedGoogle Scholar
  • 47 Andrikopoulos S, Thorburn AW, Proietto J. The New Zealand Obese Mouse: A Polygenic Model of Type 2 Diabetes. In: Sima AAF, Shafrir E. (eds.) Animal Models of Diabetes A Primer. Amsterdam: Harwood Academic; 2001: 171-183
    Google Scholar
  • 48 Igel M, Becker W, Herberg L, Joost HG. Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse. Endocrinology 1997; 138: 4234-4239
    CrossrefPubMedGoogle Scholar
  • 49 Larkins RG. Defective insulin secretory response to glucose in the New Zealand obese mouse. Improvement with restricted diet. Diabetes 1973; 22: 251-255
    CrossrefPubMedGoogle Scholar
  • 50 Lindstrom J, Peltonen M, Eriksson JG, Louheranta A, Fogelholm M, Uusitupa M, Tuomilehto J. High-fibre, low-fat diet predicts long-term weight loss and decreased type 2 diabetes risk: the Finnish Diabetes Prevention Study. Diabetologia 2006; 49: 912-920
    CrossrefPubMedGoogle Scholar
  • 51 German AJ, Holden SL, Bissot T, Morris PJ, Biourge V. A high protein high fibre diet improves weight loss in obese dogs. Vet J 2010; 183: 294-297
    CrossrefPubMedGoogle Scholar
  • 52 Reimer RA, Russell JC. Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet. Obesity (Silver Spring) 2008; 16: 40-46
    CrossrefPubMedGoogle Scholar
  • 53 Kalogeropoulou D, Lafave L, Schweim K, Gannon MC, Nuttall FQ. Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose. Metabolism 2008; 57: 1747-1752
    CrossrefPubMedGoogle Scholar
  • 54 Tovar AR, Torres N. The role of dietary protein on lipotoxicity. Biochim Biophys Acta 2009; 1801: 367-371
    PubMedGoogle Scholar
  • 55 Walther T, Dietrich N, Langhammer M, Kucia M, Hammon H, Renne U, Siems WE, Metges CC. High-protein diet in lactation leads to a sudden infant death-like syndrome in mice. PLoS One 2011; 6: e17443
    CrossrefPubMedGoogle Scholar