A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

Journal of Clinical Investigation

Volumn 126, Issue 9, 2016, Pages 3263-3278

  Maida, Adriano ^a   Zota, Annika ^a   Sjøberg, Kim A ^b   Schumacher, Jonas ^c   Sijmonsma, Tjeerd P ^c,d   Pfenninger, Anja ^e   Christensen, Marie M ^b   Gantert, Thomas ^c   Fuhrmeister, Jessica ^c   Rothermel, Ulrike ^d   Schmoll, Dieter ^e   Heikenwälder, Mathias ^d   Iovanna, Juan L ^f   Stemmer, Kerstin ^a   Kiens, Bente ^b   Herzig, Stephan ^a   Rose, Adam J ^c  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^d GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^e SANOFI AVENTIS DEUTSCHLAND GMBH   (Germany)

^f AIX MARSEILLE UNIVERSITY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYBUTYRIC ACID; ADIPONECTIN; ALANINE; ASPARTIC ACID; CARBOHYDRATE; CHOLESTEROL; FAT; FATTY ACID; FIBROBLAST GROWTH FACTOR 21; GLUCOSE; GLUTAMIC ACID; GLUTAMINE; HYDROXYPROLINE; INITIATION FACTOR 2ALPHA; INSULIN; LEPTIN; LIPID; MESSENGER RNA; NONESSENTIAL AMINO ACID; NUCLEAR PROTEIN; NUCLEAR PROTEIN 1; ORNITHINE; PROTEIN; PYRUVIC ACID; SHORT HAIRPIN RNA; SOMATOMEDIN C; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; UREA; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; DNA BINDING PROTEIN; FIBROBLAST GROWTH FACTOR; NUPR1 PROTEIN, MOUSE; P8 PROTEIN, HUMAN; PROTEIN INTAKE; TUMOR PROTEIN; UCP1 PROTEIN, HUMAN; UCP1 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY COMPOSITION; BODY HEIGHT; BODY MASS; BROWN ADIPOSE TISSUE; CALORIC INTAKE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CORE TEMPERATURE; DIETARY PROTEIN DILUTION; DILUTION; ENERGY EXPENDITURE; ENERGY METABOLISM; EXPERIMENTAL OBESITY; FATTY ACID BLOOD LEVEL; FOOD INTAKE; GENOTYPE; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; GLUCOSE TOLERANCE TEST; GLUCOSE TRANSPORT; GRIP STRENGTH; HORMONE DETERMINATION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INDIRECT CALORIMETRY; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; INSULIN SENSITIVITY; INSULIN TOLERANCE TEST; LEAN BODY WEIGHT; LIGHT DARK CYCLE; LIPID BLOOD LEVEL; LIPID DIET; LIPID STORAGE; LUNG GAS EXCHANGE; METABOLIC REGULATION; MOUSE; MUSCLE MASS; NONHUMAN; NONSHIVERING THERMOGENESIS; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; OXIDATION; OXYGEN CONSUMPTION; PHYSICAL ACTIVITY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN INTAKE; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; QUANTITATIVE ANALYSIS; RAT; RNA STABILITY; STRESS; TRIACYLGLYCEROL BLOOD LEVEL; UPREGULATION; UREA BLOOD LEVEL; UREA CYCLE; WEIGHT GAIN; ADIPOSE TISSUE; ADMINISTRATION AND DOSAGE; ADULT; ANIMAL; C57BL MOUSE; CARBOHYDRATE METABOLISM; HOMEOSTASIS; LIPID METABOLISM; LIVER; LIVER CELL; MALE; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; PHENOTYPE; TRANSGENIC MOUSE;

ADIPOSE TISSUE; ADULT; ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARBOHYDRATE METABOLISM; DIABETES MELLITUS, TYPE 2; DIETARY PROTEINS; DNA-BINDING PROTEINS; FIBROBLAST GROWTH FACTORS; GLUCOSE; HEPATOCYTES; HOMEOSTASIS; HUMANS; LIPID METABOLISM; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NEOPLASM PROTEINS; OBESITY; PHENOTYPE; UNCOUPLING PROTEIN 1;

EID: 84987784702     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI85946     Document Type: Article

References (76)

1. Popkin BM, Adair LS, Ng SW. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev. 2012;70(1):3-21
2. Ravussin E, Bogardus C. Energy balance and weight regulation: genetics versus environment. Br J Nutr. 2000;83 Suppl 1:S17-S20
3. Schutz Y. Macronutrients and energy balance in obesity. Metab Clin Exp. 1995;44(9 Suppl 3):7-11
4. Keller U. Dietary proteins in obesity and in diabetes. Int J Vitam Nutr Res. 2011;81(2-3):125-133
5. Franz MJ. Protein and diabetes: much advice, little research. Curr Diab Rep. 2002;2(5):457-464
6. Morrison CD, Reed SD, Henagan TM. Homeostatic regulation of protein intake: in search of a mechanism. Am J Physiol Regul Integr Comp Physiol. 2012;302(8):R917-R928
7. Du F, Higginbotham DA, White BD. Food intake, energy balance and serum leptin concentrations in rats fed low-protein diets. J Nutr. 2000;130(3):514-521
8. Sørensen 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(3):566-571
9. Gosby AK, et al. Testing protein leverage in lean humans: a randomised controlled experimental study. PLoS One. 2011;6(10):e25929
10. Simpson SJ, Raubenheimer D. Obesity: the protein leverage hypothesis. Obes Rev. 2005;6(2):133-142
11. Solon-Biet SM, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418-430
12. Rossetti L, Rothman DL, DeFronzo RA, Shulman GI. Effect of dietary protein on in vivo insulin action and liver glycogen repletion. Am J Physiol. 1989;257(2 Pt 1):E212-E219
13. Newgard CB, et al. A branched-chain amino acidrelated metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9(4):311-326
14. Krebs M, et al. Mechanism of amino acidinduced skeletal muscle insulin resistance in humans. Diabetes. 2002;51(3):599-605
15. van Nielen M, et al. Dietary protein intake and incidence of type 2 diabetes in Europe: the EPICInterAct Case-Cohort Study. Diabetes Care. 2014;37(7):1854-1862
16. Laeger T, et al. FGF21 is an endocrine signal of protein restriction. J Clin Invest. 2014;124(9):3913-3922
17. Tseng YH, Cypess AM, Kahn CR. Cellular bioenergetics as a target for obesity therapy. Nat Rev Drug Discov. 2010;9(6):465-482
18. Stock MJ. Gluttony and thermogenesis revisited. Int J Obes Relat Metab Disord. 1999;23(11):1105-1117
19. Frayn KN. Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(2):628-634
20. Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta. 2001;1504(1):82-106
21. Cannon B, Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2011;214(Pt 2):242-253
22. Baird TD, Wek RC. Eukaryotic initiation factor 2 phosphorylation and translational control in metabolism. Adv Nutr. 2012;3(3):307-321
23. Jin HO, et al. Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4. IUBMB Life. 2009;61(12):1153-1158
24. Averous J, et al. Amino acid deprivation regulates the stress-inducible gene p8 via the GCN2/ ATF4 pathway. Biochem Biophys Res Commun. 2011;413(1):24-29
25. Shan J, Lopez MC, Baker HV, Kilberg MS. Expression profiling after activation of amino acid deprivation response in HepG2 human hepatoma cells. Physiol Genomics. 2010;41(3):315-327
26. Jousse C, et al. TRB3 inhibits the transcriptional activation of stress-regulated genes by a negative feedback on the ATF4 pathway. J Biol Chem. 2007;282(21):15851-15861
27. Ye J, et al. GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev. 2015;29(22):2331-2336
28. Sidrauski C, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013;2:e00498
29. Sidrauski C, McGeachy AM, Ingolia NT, Walter P. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife. 2015;4:e05033
30. Goruppi S, Iovanna JL. Stress-inducible protein p8 is involved in several physiological and pathological processes. J Biol Chem. 2010;285(3):1577-1581
31. Barbosa-Sampaio HC, et al. Nupr1 deletion protects against glucose intolerance by increasing beta cell mass. Diabetologia. 2013;56(11):2477-2486
32. Kong DK, et al. Deficiency of the transcriptional regulator p8 results in increased autophagy and apoptosis, and causes impaired heart function. Mol Biol Cell. 2010;21(8):1335-1349
33. Nässl AM, Rubio-Aliaga I, Fenselau H, Marth MK, Kottra G, Daniel H. Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1. Am J Physiol Gastrointest Liver Physiol. 2011;301(1):G128-G137
34. Bielohuby M, et al. Impaired glucose tolerance in rats fed low-carbohydrate, highfat diets. Am J Physiol Endocrinol Metab. 2013;305(9):E1059-E1070
35. Dushay JR, Toschi E, Mitten EK, Fisher FM, Herman MA, Maratos-Flier E. Fructose ingestion acutely stimulates circulating FGF21 levels in humans. Mol Metab. 2015;4(1):51-57
36. Gimeno RE, Moller DE. FGF21-based pharmacotherapy-potential utility for metabolic disorders. Trends Endocrinol Metab. 2014;25(6):303-311
37. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab. 2000;2(6):345-350
38. Jungas RL, Halperin ML, Brosnan JT. Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev. 1992;72(2):419-448
39. Perry RJ, et al. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell. 2015;160(4):745-758
40. Mittelman SD, Fu YY, Rebrin K, Steil G, Bergman RN. Indirect effect of insulin to suppress endogenous glucose production is dominant, even with hyperglucagonemia. J Clin Invest. 1997;100(12):3121-3130
41. Cooney GJ, Astbury LD, Williams PF, Caterson ID. Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose. Diabetes. 1987;36(2):152-158
42. Jiang Y, et al. Mice lacking neutral amino acid transporter B(0)AT1 (Slc6a19) have elevated levels of FGF21 and GLP-1 and improved glycaemic control. Mol Metab. 2015;4(5):406-417
43. Owen BM, Mangelsdorf DJ, Kliewer SA. Tissuespecific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol Metab. 2015;26(1):22-29
44. Lees EK, et al. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor. Aging Cell. 2014;13(5):817-827
45. Stone KP, Wanders D, Orgeron M, Cortez CC, Gettys TW. Mechanisms of increased in vivo insulin sensitivity by dietary methionine restriction in mice. Diabetes. 2014;63(11):3721-3733
46. De Sousa-Coelho AL, et al. FGF21 mediates the lipid metabolism response to amino acid starvation. J Lipid Res. 2013;54(7):1786-1797
47. Fisher FM, et al. Fibroblast growth factor 21 limits lipotoxicity by promoting hepatic fatty acid activation in mice on methionine and choline-deficient diets. Gastroenterology. 2014;147(5):1073-1083.e6
48. Cornu M, et al. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21. Proc Natl Acad Sci USA. 2014;111(32):11592-11599
49. Wilson GJ, et al. GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment. Am J Physiol Endocrinol Metab. 2015;308(4):E283-E293
50. Shimizu N, et al. A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling. Nat Commun. 2015;6:6693
51. Cano CE, Hamidi T, Sandi MJ, Iovanna JL. Nupr1: the Swiss-knife of cancer. J Cell Physiol. 2011;226(6):1439-1443
52. Wanders D, et al. Role of GCN2-independent signaling through a noncanonical PERK/ NRF2 pathway in the physiological responses to dietary methionine restriction. Diabetes. 2016;65(6):1499-1510
53. Rothwell NJ, Stock MJ, Tyzbir RS. Energy balance and mitochondrial function in liver and brown fat of rats fed "cafeteria" diets of varying protein content. J Nutr. 1982;112(9):1663-1672
54. Rothwell NJ, Stock MJ. A role for brown adipose tissue in diet-induced thermogenesis. Nature. 1979;281(5726):31-35
55. Stock MJ, Rothwell NJ. The role of brown fat in diet-induced thermogenesis. Int J Vitam Nutr Res. 1986;56(2):205-210
56. Specter SE, Hamilton JS, Stern JS, Horwitz BA. Chronic protein restriction does not alter energetic efficiency or brown adipose tissue thermogenic capacity in genetically obese (fa/fa) Zucker rats. J Nutr. 1995;125(8):2183-2193
57. Wanders D, et al. UCP1 is an essential mediator of the effects of methionine restriction on energy balance but not insulin sensitivity. FASEB J. 2015;29(6):2603-2615
58. Kim JY, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621-2637
59. Renne U, et al. Lifelong obesity in a polygenic mouse model prevents age-and dietinduced glucose intolerance-obesity is no road to late-onset diabetes in mice. PLoS One. 2013;8(11):e79788
60. Sun K, Tordjman J, Clément K, Scherer PE. Fibrosis and adipose tissue dysfunction. Cell Metab. 2013;18(4):470-477
61. Blüher M. The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol. 2010;21(1):38-43
62. Miller DS, Payne PR. Longevity and protein intake. Exp Gerontol. 1968;3(3):231-234
63. Levine ME, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19(3):407-417
64. Parrella E, et al. Protein restriction cycles reduce IGF-1 and phosphorylated Tau, and improve behavioral performance in an Alzheimer's disease mouse model. Aging Cell. 2013;12(2):257-268
65. Harputlugil E, Hine C, Vargas D, Robertson L, Manning BD, Mitchell JR. The TSC complex is required for the benefits of dietary protein restriction on stress resistance in vivo. Cell Rep. 2014;8(4):1160-1170
66. Sadagurski M, White MF. Integrating metabolism and longevity through insulin and IGF1 signaling. Endocrinol Metab Clin North Am. 2013;42(1):127-148
67. Zhang Y, et al. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Elife. 2012;1:e00065
68. Speakman JR. Body size, energy metabolism and lifespan. J Exp Biol. 2005;208(Pt 9):1717-1730
69. Enerbäck S, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997;387(6628):90-94
70. Hotta Y, et al. Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver. Endocrinology. 2009;150(10):4625-4633
71. Vasseur S, et al. p8-deficient fibroblasts grow more rapidly and are more resistant to adriamycin-induced apoptosis. Oncogene. 2002;21(11):1685-1694
72. Stettner P, et al. Sulfatides are required for renal adaptation to chronic metabolic acidosis. Proc Natl Acad Sci USA. 2013;110(24):9998-10003
73. Ayala JE, et al. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech. 2010;3(9-10):525-534
74. Maarbjerg SJ, et al. Genetic impairment of AMPKalpha2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Am J Physiol Endocrinol Metab. 2009;297(4):E924-E934
75. Deschatrette J, Weiss MC. Characterization of differentiated and dedifferentiated clones from a rat hepatoma. Biochimie. 1974;56(11-12):1603-1611
76. Klingmüller U, et al. Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways. Syst Biol (Stevenage). 2006;153(6):433-447