Dietary Modulation of Circulating Leptin Levels: Site-Specific Changes in Fat Deposition and Ob mRNA Expression

Abstract

In order to study the effects of diet on fat distribution, circulating leptin levels and ob mRNA expression, diets of different macronutrient composition were fed to lean mice and gold thioglucose-obese mice. A high-fat diet and 2 high-carbohydrate diets, one containing mostly high-glycaemic-index starch and the other containing low-glycaemic-index starch were fed ad libitum for 10 weeks and were compared to standard laboratory chow. Weight gain was attenuated by feeding low-glycaemic-index starch in all mice and by feeding a high-fat diet in lean mice. Reduced adiposity was seen in lean mice fed low-glycaemic-index starch, whereas increased adiposity was seen in both lean and obese mice fed on the high-fat diet. Circulating leptin levels, when corrected for adiposity, were decreased in all mice fed either the high-fat diet or the low-GI diet. In epididymal fat pads, decreased ob mRNA expression was seen after both high-fat and high-glycaemic-index starch feeding. These results show that diet macronutrient composition contributes to the variability of circulating leptin levels by the combined effects of diet on fat distribution and on site-specific changes in ob mRNA expression.

Key words

Macronutrient Composition - Glycaemic Index - Obesity - Insulin Resistance

• 1 Maffei M, Halaas J, Ravussin E, Pratley R E, Lee G H, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern P, Friedman J M. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight reduced subjects.  Nat Med. 1995;  1 1155-1161
• 2 Coleman R A, Herrmann T S. Nutritional regulation of leptin in humans.  Diabetologia. 1999;  42 639-646
• 3 Havel P J, Townsend R, Chaump L, Teff K. High-fat meals reduce 24-h circulating leptin concentrations in women.  Diabetes. 1999;  48 334-341
• 4 Romon M, Lebel P, Velly C, Marecaux N, Fruchart J C, Dallongeville J. Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake.  Am J Physiol. 1999;  277 E855-E861
• 5 Havel P J, Kasim-Karakas S, Mueller W, Johnson P R, Gingerich R L, Stern J S. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss.  J Clin Endocrinol Metab. 1996;  81 4406-4413
• 6 Weigle D S, Duell P B, Connor W E, Steiner R A, Soules M R, Kuijper J L. Effect of fasting, refeeding and dietary fat restriction on plasma leptin levels.  J Clin Endocrinol Metab. 1997;  82 561-565
• 7 Ahren B, Mansson S, Gingerich R L, Havel P J. Regulation of plasma leptin in mice: influence of age, high-fat diet and fasting.  Am J Physiol. 1997;  273 R113-R120
• 8 Buettner R, Newgard C B, Rhodes C J, O’Doherty R M. Correction of diet-induced hyperglycemia, hyperinsulinemia and skeletal muscle insulin resistance by moderate hyperleptinemia.  Am J Physiol. 2000;  278 E563-E569
• 9 Chavez M, Seeley R J, Havel P J, Friedman M I, Matson C A, Woods S C. Effect of a high-fat diet on food intake and hypothalamic neuropeptide gene expression in streptozotocin diabetes.  J Clin Invest. 1998;  102 340-346
• 10 Ainslie D A, Proietto J, Fam B C, Thorburn A W. Short-term, high fat diets lower circulating leptin concentrations in rats.  Am J Clin Nutr. 2000;  71 438-443
• 11 Surwit R S, Petro A E, Parekh P, Collins S. Low plasma leptin in response to dietary fat in diabetes and obesity prone mice.  Diabetes. 1997;  46 1516-1520
• 12 Jenkins A B, Markovic T P, Fleury A, Campbell L V. Carbohydrate intake and short-term regulation of leptin in humans.  Diabetologia. 1997;  40 348-351
• 13 Agus M SD, Swain J F, Larson C L, Eckert E A, Ludwig D S. Dietary composition and physiologic adaptations to energy restriction.  Am J Clin Nutr. 2000;  71 901-907
• 14 Raben A, Astrup A. Leptin is influenced both by predisposition to obesity and diet composition.  Int J Obesity. 2000;  24 450-459
• 15 Harte R A, Kirk E A, Rosenfeld M E, LeBouef R C. Initiation of hyperinsulinemia and hyperleptinemia is diet dependent in C57BL/6 mice.  Horm Metab Res. 1999;  31 570-575
• 16 Pawlak D B, Bryson J M, Denyer G S, Brand-Miller J C. High glycemic index starch promotes hypersecretion of insulin and higher body fat in rats without changes in insulin sensitivity.  J Nutr. 2001;  131 99-104
• 17 Suga S, Hirano T, Kageyama H, Osaka T, Namba Y, Tsuji M, Miura M, Adachi M, Inoue S. Effects of fructose and glucose on plasma leptin, insulin and insulin resistance in lean and VMH-lesioned obese rats.  Am J Physiol. 2000;  278 E677-E683
• 18 Mizuno T, Bergen H, Kleopoulos S, Bauman W A, Mobbs C V. Effects of nutritional status and aging on leptin gene expression in mice: importance of glucose.  Horm Metab Res. 1996;  28 679-684
• 19 Du F, Higginbotham D A, White B D. Food intake, energy balance and serum leptin concentrations in rats fed low-protein diets.  J Nutr. 2000;  130 514-521
• 20 Mizuno T M, Bergen H, Funabashi T, Kleopoulos S P, Zhong Y G, Bauman W A, Mobbs C V. Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.  Proc Natl Acad Sci USA. 1996;  93 3434-3438
• 21 Saladin R, de Vos P, Guerre-Milo M, Leturque A, Girard J, Staels B, Auwerx J. Transient increase in obese gene expression after food intake or insulin administration.  Nature. 1995;  377 527-529
• 22 Raclot T, Groscolas R, Langin D, Ferre P. Site-specific regulation of gene expression by n-3 polyunsaturated fatty acids in rat white adipose tissues.  J Lipid Res. 1997;  38 1963-1972
• 23 Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat.  Nature. 1998;  393 684-688
• 24 Hube F, Lietz U. Igel M, Jensen PB, Tornqvist H, Joost H-G, Hauner H. Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans.  Horm Metab Res. 1996;  28 690-693
• 25 Montague C T, Prins J B, Sanders L, Digby J E, O’Rahilly S. Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution.  Diabetes. 1997;  46 342-347
• 26 Lerer-Metzger M, Rizkalla S W, Luo J, Champ M, Kabir M, Bruzzo F, Bornet F, Slama G. Effects of long-term low-glycaemic index starchy food on plasma glucose and lipid concentrations and adipose tissue cellularity in normal and diabetic rats.  Br J Nutr. 1996;  75 723-732
• 27 Byrnes S E, Brand Miller J C, Denyer G S. Amylopectin starch promotes the development of insulin resistance in rats.  J Nutr. 1995;  125 1430-1437
• 28 Bryson J M, Phuyal J L, Proctor D R, Blair S C, Caterson I D, Cooney G J. Plasma insulin rise precedes rise in ob mRNA and plasma leptin in gold thioglucose-obese mice.  Am J Physiol. 1999;  276 E358-E364
• 29 Rousseau V, Becker D J, Ongemba L N, Rahier J, Henquin J-C, Brichard S M. Developmental and nutritional changes of ob and PPAR γ2 gene expression in rat white adipose tissue.  Biochem J. 1997;  320 451-456
• 30 Bryson J M, Phuyal J L, Swan V, Caterson I D. Leptin has acute effects on glucose and lipid metabolism in both lean and gold thioglucose-obese mice.  Am J Physiol. 1999;  277 E417-E422
• 31 Wang J, Liu R, Liu L, Chowdhury R, Barzilai N, Tan J, Rossetti L. The effects of leptin on Lep expression is tissue-specific and nutritionally regulated.  Nat Med. 1999;  5 895-899
• 32 Kabir M, Guerre-Millo M, Laromiguiere M, Slama G, Rizkalla S W. Negative regulation of leptin by chronic high-glycemic index starch diet.  Metabolism. 2000;  49 764-769
• 33 Barr V A, Malide D, Zarnowski M J, Taylor S I, Cushman S W. Insulin stimulates both leptin secretion and production by rat white adipose tissue.  Endocrinology. 1997;  138 4463-4472
• 34 Mueller W M, Gregoire F M, Stanhope K L, Mobbs C V, Mizuno T M, Warden C H, Stern J S, Havel P J. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.  Endocrinology. 1998;  139 551-558
• 35 Cusin I, Sainsbury A, Doyle P, Rohner-Jeanrenaud F, Jeanrenaud B. The ob gene and insulin. A relationship leading to clues to the understanding of obesity.  Diabetes. 1995;  44 1467-1470
• 36 Bradley R L, Cheatham B. Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes.  Diabetes. 1999;  48 272-278
• 37 Halleux C M, Servais I, Reul B A, Detry R, Brichard S M. Multihormonal control of ob gene expression and leptin secretion from culture human visceral adipose tissue: increased responsiveness to glucocorticoids in obesity.  J Clin Endocrinol Metab. 1998;  83 902-910
• 38 Zhang H H, Kumar S, Barnett A H, Eggo M C. Intrinsic site-specific differences in the expression of leptin in human adipocytes and its autocrine effects on glucose uptake.  J Clin Endocrinol Metab. 1999;  84 2550-2556