Skip to main content

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring

  • Mariana M. Almeida (a1), Camilla P. Dias-Rocha (a1), André S. Souza (a1), Mariana F. Muros (a1), Leonardo S. Mendonca (a2), Carmen C. Pazos-Moura (a1) and Isis H. Trevenzoli (a1)...

Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS’s components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

Corresponding author
* Corresponding author: I. H. Trevenzoli, email
Hide All

These authors contributed equally to this study.

Hide All
1. Burgio, E, Lopomo, A & Migliore, L (2015) Obesity and diabetes: from genetics to epigenetics. Mol Biol Rep 42, 799818.
2. Stang, J & Huffman, LG (2016) Position of the Academy of Nutrition and Dietetics: obesity, reproduction, and pregnancy outcomes. J Acad Nutr Diet 116, 677691.
3. Langley-Evans, SC (2015) Nutrition in early life and the programming of adult disease: a review. J Hum Nutr Diet 28, Suppl. 1, 114.
4. Ma, X, Lee, P, Chisholm, DJ, et al. (2015) Control of adipocyte differentiation in different fat depots; implications for pathophysiology or therapy. Front Endocrinol (Lausanne) 6, 1.
5. Ibrahim, MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11, 1118.
6. Pellegrinelli, V, Carobbio, S & Vidal-Puig, A (2016) Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 59, 10751088.
7. Labbe, SM, Caron, A, Lanfray, D, et al. (2015) Hypothalamic control of brown adipose tissue thermogenesis. Front Syst Neurosci 9, 150.
8. Kooijman, S, van den Heuvel, JK & Rensen, PC (2015) Neuronal control of brown fat activity. Trends Endocrinol Metab 26, 657668.
9. Saito, M, Yoneshiro, T & Matsushita, M (2016) Activation and recruitment of brown adipose tissue by cold exposure and food ingredients in humans. Best Pract Res Clin Endocrinol Metab 30, 537547.
10. Hepler, C, Vishvanath, L & Gupta, RK (2017) Sorting out adipocyte precursors and their role in physiology and disease. Genes Dev 31, 127140.
11. Wankhade, UD, Shen, M, Yadav, H, et al. (2016) Novel browning agents, mechanisms, and therapeutic potentials of brown adipose tissue. Biomed Res Int 2016, 2365609.
12. Rocha-Rodrigues, S, Rodriguez, A, Gouveia, AM, et al. (2016) Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sci 165, 100108.
13. Cohen, P & Spiegelman, BM (2015) Brown and beige fat: molecular parts of a thermogenic machine. Diabetes 64, 23462351.
14. Cristino, L, Becker, T & Di Marzo, V (2014) Endocannabinoids and energy homeostasis: an update. Biofactors 40, 389397.
15. D’Addario, C, Micioni Di Bonaventura, MV, Pucci, M, et al. (2014) Endocannabinoid signaling and food addiction. Neurosci Biobehav Rev 47, 203224.
16. Matias, I & Di Marzo, V (2007) Endocannabinoids and the control of energy balance. Trends Endocrinol Metab 18, 2737.
17. Maccarrone, M, Bab, I, Biro, T, et al. (2015) Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci 36, 277296.
18. Krentz, AJ, Fujioka, K & Hompesch, M (2016) Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles. Diabetes Obes Metab 18, 558570.
19. Keimpema, E, Calvigioni, D & Harkany, T (2013) Endocannabinoid signals in the developmental programming of delayed-onset neuropsychiatric and metabolic illnesses. Biochem Soc Trans 41, 15691576.
20. D’Asti, E, Long, H, Tremblay-Mercier, J, et al. (2010) Maternal dietary fat determines metabolic profile and the magnitude of endocannabinoid inhibition of the stress response in neonatal rat offspring. Endocrinology 151, 16851694.
21. Ramirez-Lopez, MT, Arco, R, Decara, J, et al. (2016) Exposure to a highly caloric palatable diet during the perinatal period affects the expression of the endogenous cannabinoid system in the brain, liver and adipose tissue of adult rat offspring. PLOS ONE 11, e0165432.
22. Ramirez-Lopez, MT, Arco, R, Decara, J, et al. (2016) Long-term effects of prenatal exposure to undernutrition on cannabinoid receptor-related behaviors: sex and tissue-specific alterations in the mRNA expression of cannabinoid receptors and lipid metabolic regulators. Front Behav Neurosci 10, 241.
23. Ramirez-Lopez, MT, Vazquez, M, Bindila, L, et al. (2015) Exposure to a highly caloric palatable diet during pregestational and gestational periods affects hypothalamic and hippocampal endocannabinoid levels at birth and induces adiposity and anxiety-like behaviors in male rat offspring. Front Behav Neurosci 9, 339.
24. Franco, JG, Fernandes, TP, Rocha, CP, et al. (2012) Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning. J Physiol 590, 55035518.
25. Freitas, HR, Isaac, AR, Malcher-Lopes, R, et al. (2017) Polyunsaturated fatty acids and endocannabinoids in health and disease. Nutr Neurosci 7, 120.
26. Kim, J, Carlson, ME, Kuchel, GA, et al. (2016) Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice. Int J Obes (Lond) 40, 129137.
27. Buettner, C, Muse, ED, Cheng, A, et al. (2008) Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med 14, 667675.
28. Cristino, L, Busetto, G, Imperatore, R, et al. (2013) Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. Proc Natl Acad Sci U S A 110, E2229E2238.
29. Cristino, L, Luongo, L, Imperatore, R, et al. (2016) Orexin-A and endocannabinoid activation of the descending antinociceptive pathway underlies altered pain perception in leptin signaling deficiency. Neuropsychopharmacology 41, 508520.
30. Proto, MC, Gazzerro, P, Di Croce, L, et al. (2012) Interaction of endocannabinoid system and steroid hormones in the control of colon cancer cell growth. J Cell Physiol 227, 250258.
31. Lee, KS, Asgar, J, Zhang, Y, et al. (2013) The role of androgen receptor in transcriptional modulation of cannabinoid receptor type 1 gene in rat trigeminal ganglia. Neuroscience 254, 395403.
32. Waleh, NS, Cravatt, BF, Apte-Deshpande, A, et al. (2002) Transcriptional regulation of the mouse fatty acid amide hydrolase gene. Gene 291, 203210.
33. Maia, J, Almada, M, Silva, A, et al. (2017) The endocannabinoid system expression in the female reproductive tract is modulated by estrogen. J Steroid Biochem Mol Biol (epublication ahead of print version 22 July 2017).
34. Grimaldi, P, Pucci, M, Di Siena, S, et al. (2012) The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1. Cell Mol Life Sci 69, 41774190.
35. Drummond, GB (2009) Reporting ethical matters in the Journal of Physiology: standards and advice. J Physiol 587, 713719.
36. Marques, RG, Morales, MM & Petroianu, A (2009) Brazilian law for scientific use of animals. Acta Cir Bras 24, 6974.
37. Reeves, PG, Nielsen, FH & Fahey, GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123, 19391951.
38. Fischbeck, KL & Rasmussen, KM (1987) Effect of repeated reproductive cycles on maternal nutritional status, lactational performance and litter growth in ad libitum-fed and chronically food-restricted rats. J Nutr 117, 19671975.
39. Faul, F, Erdfelder, E, Lang, AG, et al. (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39, 175191.
40. Oliveira, LS, Souza, LL, Souza, AF, et al. (2016) Perinatal maternal high-fat diet promotes alterations in hepatic lipid metabolism and resistance to the hypolipidemic effect of fish oil in adolescent rat offspring. Mol Nutr Food Res 60, 24932504.
41. Lopez-Jaramillo, P, Gomez-Arbelaez, D, Lopez-Lopez, J, et al. (2014) The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Horm Mol Biol Clin Investig 18, 3745.
42. Ahima, RS (2011) Digging deeper into obesity. J Clin Invest 121, 20762079.
43. Nakano, Y, Itabashi, K, Sakurai, M, et al. (2014) Accumulation of subcutaneous fat, but not visceral fat, is a predictor of adiponectin levels in preterm infants at term-equivalent age. Early Hum Dev 90, 213217.
44. Hansen-Pupp, I, Hellgren, G, Hard, AL, et al. (2015) Early surge in circulatory adiponectin is associated with improved growth at near term in very preterm infants. J Clin Endocrinol Metab 100, 23802387.
45. Friedman, JM & Halaas, JL (1998) Leptin and the regulation of body weight in mammals. Nature 395, 763770.
46. Lecoutre, S, Deracinois, B, Laborie, C, et al. (2016) Depot- and sex-specific effects of maternal obesity in offspring’s adipose tissue. J Endocrinol 230, 3953.
47. Desai, M, Jellyman, JK, Han, G, et al. (2014) Maternal obesity and high-fat diet program offspring metabolic syndrome. Am J Obstet Gynecol 211, 237.e1237.e13.
48. Franco, JG, Dias-Rocha, CP, Fernandes, TP, et al. (2016) Resveratrol treatment rescues hyperleptinemia and improves hypothalamic leptin signaling programmed by maternal high-fat diet in rats. Eur J Nutr 55, 601610.
49. Bjorbaek, C (2009) Central leptin receptor action and resistance in obesity. J Investig Med 57, 789794.
50. Iannotti, FA, Piscitelli, F, Martella, A, et al. (2013) Analysis of the ‘endocannabinoidome’ in peripheral tissues of obese Zucker rats. Prostaglandins Leukot Essent Fatty Acids 89, 127135.
51. Bennetzen, MF, Nielsen, TS, Paulsen, SK, et al. (2010) Reduced cannabinoid receptor 1 protein in subcutaneous adipose tissue of obese. Eur J Clin Invest 40, 121126.
52. Bluher, M, Engeli, S, Kloting, N, et al. (2006) Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 55, 30533060.
53. Bordicchia, M, Battistoni, I, Mancinelli, L, et al. (2010) Cannabinoid CB1 receptor expression in relation to visceral adipose depots, endocannabinoid levels, microvascular damage, and the presence of the Cnr1 A3813G variant in humans. Metabolism 59, 734741.
54. Cardinal, P, Bellocchio, L, Clark, S, et al. (2012) Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology 153, 41364143.
55. Jelsing, J, Larsen, PJ & Vrang, N (2009) The effect of leptin receptor deficiency and fasting on cannabinoid receptor 1 mRNA expression in the rat hypothalamus, brainstem and nodose ganglion. Neurosci Lett 463, 125129.
56. Armitage, JA, Poston, L & Taylor, PD (2008) Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity. Front Horm Res 36, 7384.
57. Fonseca, BM, Correia-da-Silva, G, Taylor, AH, et al. (2012) Characterisation of the endocannabinoid system in rat haemochorial placenta. Reprod Toxicol 34, 347356.
58. Wu, J, Gouveia-Figueira, S, Domellof, M, et al. (2016) Oxylipins, endocannabinoids, and related compounds in human milk: Levels and effects of storage conditions. Prostaglandins Other Lipid Mediat 122, 2836.
59. Vaswani, K, Chan, HW, Peiris, HN, et al. (2015) Gestation related gene expression of the endocannabinoid pathway in rat placenta. Mediators Inflamm 2015, 850471.
60. Aguirre, CA, Castillo, VA & Llanos, MN (2012) Excess of the endocannabinoid anandamide during lactation induces overweight, fat accumulation and insulin resistance in adult mice. Diabetol Metab Syndr 4, 35.
61. Aguirre, CA, Castillo, VA & Llanos, MN (2015) The endocannabinoid anandamide during lactation increases body fat content and CB1 receptor levels in mice adipose tissue. Nutr Diabetes 5, e167.
62. Henry, RJ, Kerr, DM, Flannery, LE, et al. (2017) Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: an effect partially mediated by central TRPV1. Brain Behav Immun 62, 318331.
63. Engeli, S, Bohnke, J, Feldpausch, M, et al. (2005) Activation of the peripheral endocannabinoid system in human obesity. Diabetes 54, 28382843.
64. Murdolo, G, Kempf, K, Hammarstedt, A, et al. (2007) Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals. J Endocrinol Invest 30, RC17RC21.
65. Cable, JC, Tan, GD, Alexander, SP, et al. (2011) The activity of the endocannabinoid metabolising enzyme fatty acid amide hydrolase in subcutaneous adipocytes correlates with BMI in metabolically healthy humans. Lipids Health Dis 10, 129.
66. Silvestri, C & Di Marzo, V (2013) The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab 17, 475490.
67. Tang, QQ, Gronborg, M, Huang, H, et al. (2005) Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and glycogen synthase kinase 3beta is required for adipogenesis. Proc Natl Acad Sci U S A 102, 97669771.
68. Gaggini, M, Saponaro, C & Gastaldelli, A (2015) Not all fats are created equal: adipose vs. ectopic fat, implication in cardiometabolic diseases. Horm Mol Biol Clin Investig 22, 718.
69. Jourdan, T, Djaouti, L, Demizieux, L, et al. (2010) CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice. Diabetes 59, 926934.
70. Shanik, MH, Xu, Y, Skrha, J, et al. (2008) Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care 31, S262S268.
71. Juan, CC, Chen, KH, Wang, PH, et al. (2015) Endocannabinoid system activation may be associated with insulin resistance in women with polycystic ovary syndrome. Fertil Steril 104, 200206.
72. Pagano, C, Pilon, C, Calcagno, A, et al. (2007) The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J Clin Endocrinol Metab 92, 48104819.
73. Okuno, A, Tamemoto, H, Tobe, K, et al. (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 101, 13541361.
74. Zhang, J, Fu, M, Cui, T, et al. (2004) Selective disruption of PPARgamma 2 impairs the development of adipose tissue and insulin sensitivity. Proc Natl Acad Sci U S A 101, 1070310708.
75. Medina-Gomez, G, Virtue, S, Lelliott, C, et al. (2005) The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform. Diabetes 54, 17061716.
76. Johnson, JA, Trasino, SE, Ferrante, AW Jr, et al. (2007) Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats. Obesity (Silver Spring) 15, 26532663.
77. Li, KK, Liu, CL, Shiu, HT, et al. (2016) Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes. Sci Rep 6, 20172.
78. Song, Y, Kim, MB, Kim, C, et al. (2016) 5,7-dimethoxyflavone attenuates obesity by inhibiting adipogenesis in 3T3-L1 adipocytes and high-Fat diet-induced obese C57BL/6J mice. J Med Food 19, 11111119.
79. Sharma, BR, Oh, J, Kim, HA, et al. (2015) Anti-obesity effects of the mixture of eriobotrya japonica and nelumbo nucifera in adipocytes and high-fat diet-induced obese mice. Am J Chin Med 43, 681694.
80. Bluher, M (2013) Importance of estrogen receptors in adipose tissue function. Mol Metab 2, 130132.
81. Heine, PA, Taylor, JA, Iwamoto, GA, et al. (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci U S A 97, 1272912734.
82. Barros, RP, Gabbi, C, Morani, A, et al. (2009) Participation of ERalpha and ERbeta in glucose homeostasis in skeletal muscle and white adipose tissue. Am J Physiol Endocrinol Metab 297, E124E133.
83. Foryst-Ludwig, A, Clemenz, M, Hohmann, S, et al. (2008) Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a negative cross-talk with PPARgamma. PLoS Genet 4, e1000108.
84. Weigt, C, Hertrampf, T, Zoth, N, et al. (2012) Impact of estradiol, ER subtype specific agonists and genistein on energy homeostasis in a rat model of nutrition induced obesity. Mol Cell Endocrinol 351, 227238.
85. Pasquarelli, N, Porazik, C, Hanselmann, J, et al. (2015) Comparative biochemical characterization of the monoacylglycerol lipase inhibitor KML29 in brain, spinal cord, liver, spleen, fat and muscle tissue. Neuropharmacology 91, 148156.
86. Vander Tuig, JG, Kerner, J & Romsos, DR (1985) Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats. Am J Physiol 248, E607E617.
87. Wagner, IV, Perwitz, N, Drenckhan, M, et al. (2011) Cannabinoid type 1 receptor mediates depot-specific effects on differentiation, inflammation and oxidative metabolism in inguinal and epididymal white adipocytes. Nutr Diabetes 1, e16.
88. Soethoudt, M, Grether, U, Fingerle, J, et al. (2017) Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity. Nat Commun 8, 13958.
89. Verty, AN, Stefanidis, A, McAinch, AJ, et al. (2015) Anti-obesity effect of the CB2 receptor agonist JWH-015 in diet-induced obese mice. PLOS ONE 10, e0140592.
90. Chiurchiu, V, Lanuti, M, Catanzaro, G, et al. (2014) Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor. Atherosclerosis 233, 5563.
91. Ueda, Y, Miyagawa, N & Wakitani, K (2007) Involvement of cannabinoid CB2 receptors in the IgE-mediated triphasic cutaneous reaction in mice. Life Sci 80, 414419.
92. Deveaux, V, Cadoudal, T, Ichigotani, Y, et al. (2009) Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS ONE 4, e5844.
93. Di Marzo, V (2008) The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 51, 13561367.
94. Sarzani, R, Bordicchia, M, Marcucci, P, et al. (2009) Altered pattern of cannabinoid type 1 receptor expression in adipose tissue of dysmetabolic and overweight patients. Metabolism 58, 361367.
95. Bennetzen, MF, Wellner, N, Ahmed, SS, et al. (2011) Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss. Int J Obes (Lond) 35, 13771384.
96. Engeli, S, Lehmann, AC, Kaminski, J, et al. (2014) Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects. Obesity (Silver Spring) 22, E70E76.
97. Krott, LM, Piscitelli, F, Heine, M, et al. (2016) Endocannabinoid regulation in white and brown adipose tissue following thermogenic activation. J Lipid Res 57, 464473.
98. Zou, T, Chen, D, Yang, Q, et al. (2017) Resveratrol supplementation of high-fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. J Physiol 595, 15471562.
99. Geurts, L, Everard, A, Van Hul, M, et al. (2015) Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota. Nat Commun 6, 6495.
100. Quarta, C, Bellocchio, L, Mancini, G, et al. (2010) CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance. Cell Metab 11, 273285.
101. de Almeida, DL, Fabricio, GS, Trombini, AB, et al. (2013) Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in rats. Cell Physiol Biochem 32, 16211630.
102. Liang, X, Yang, Q, Zhang, L, et al. (2016) Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice. Sci Rep 6, 34345.
103. Verty, AN, Allen, AM & Oldfield, BJ (2009) The effects of rimonabant on brown adipose tissue in rat: implications for energy expenditure. Obesity (Silver Spring) 17, 254261.
104. Hsiao, WC, Shia, KS, Wang, YT, et al. (2015) A novel peripheral cannabinoid receptor 1 antagonist, BPR0912, reduces weight independently of food intake and modulates thermogenesis. Diabetes Obes Metab 17, 495504.
105. Boon, MR, Kooijman, S, van Dam, AD, et al. (2014) Peripheral cannabinoid 1 receptor blockade activates brown adipose tissue and diminishes dyslipidemia and obesity. FASEB J 28, 53615375.
106. Lettieri Barbato, D, Tatulli, G, Vegliante, R, et al. (2015) Dietary fat overload reprograms brown fat mitochondria. Front Physiol 6, 272.
107. Townsend, KL & Tseng, YH (2014) Brown fat fuel utilization and thermogenesis. Trends Endocrinol Metab 25, 168177.
108. Lopez, M & Tena-Sempere, M (2016) Estradiol and brown fat. Best Pract Res Clin Endocrinol Metab 30, 527536.
109. Lillycrop, KA & Burdge, GC (2015) Maternal diet as a modifier of offspring epigenetics. J Dev Orig Health Dis 6, 8895.
110. Benkalfat, NB, Merzouk, H, Bouanane, S, et al. (2011) Altered adipose tissue metabolism in offspring of dietary obese rat dams. Clin Sci (Lond) 121, 1928.
111. D’Addario, C, Di Francesco, A, Pucci, M, et al. (2013) Epigenetic mechanisms and endocannabinoid signalling. FEBS J 280, 19051917.
112. Yamamoto, Y, Gesta, S, Lee, KY, et al. (2010) Adipose depots possess unique developmental gene signatures. Obesity (Silver Spring) 18, 872878.
113. Breton, C (2013) The hypothalamus-adipose axis is a key target of developmental programming by maternal nutritional manipulation. J Endocrinol 216, R19R31.
114. Valencak, TG, Osterrieder, A & Schulz, TJ (2017) Sex matters: the effects of biological sex on adipose tissue biology and energy metabolism. Redox Biol 12, 806813.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 26
Total number of PDF views: 127 *
Loading metrics...

Abstract views

Total abstract views: 459 *
Loading metrics...

* Views captured on Cambridge Core between 7th November 2017 - 22nd March 2018. This data will be updated every 24 hours.