A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

Adiposity Energy restriction Erythropoietin Ketone bodies Nutritional ketosis

Journal

Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594

Informations de publication

Date de publication:
02 May 2024
Historique:
received: 01 12 2023
accepted: 14 03 2024
medline: 2 5 2024
pubmed: 2 5 2024
entrez: 2 5 2024
Statut: aheadofprint

Résumé

Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. β-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months. It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

Identifiants

DOI: 10.1007/s40618-024-02364-9 PMID: 38696124
pubmed: 38696124
doi: 10.1007/s40618-024-02364-9
pii: 10.1007/s40618-024-02364-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Instituto de Salud Carlos III
ID : PI20/00650
Organisme : Instituto de Salud Carlos III
ID : PI20/00628
Organisme : Instituto de Salud Carlos III
ID : CP17/00088
Organisme : Instituto de Salud Carlos III
ID : CPII22/00008
Organisme : Consellería de Economía, Emprego e Industria, Xunta de Galicia
ID : IN607B2020/09
Organisme : Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia
ID : IN606-2020/013

Informations de copyright

© 2024. The Author(s).

Références

Risk Factor Collaboration NCD, (NCD-RisC), (2019) Rising rural body-mass index is the main driver of the global obesity epidemic in adults. Nature 569:260–264. https://doi.org/10.1038/s41586-019-1171-x
doi: 10.1038/s41586-019-1171-x
Lorenzo PM, Crujeiras AB (2021) Potential effects of nutrition-based weight loss therapies in reversing obesity-related breast cancer epigenetic marks. Food Funct 12:1402–1414. https://doi.org/10.1039/d0fo01984d
doi: 10.1039/d0fo01984d pubmed: 33480953
Jelkmann W (1992) Erythropoietin: structure, control of production, and function. Physiol Rev 72:449–489. https://doi.org/10.1152/physrev.1992.72.2.449
doi: 10.1152/physrev.1992.72.2.449 pubmed: 1557429
Semenza GL (2009) Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis. Blood 114:2015–2019. https://doi.org/10.1182/blood-2009-05-189985
doi: 10.1182/blood-2009-05-189985 pubmed: 19494350
Schneider A, Schneider MP, Scharnagl H et al (2013) Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes. BMC Nephrol 14:67. https://doi.org/10.1186/1471-2369-14-67
doi: 10.1186/1471-2369-14-67 pubmed: 23521816 pmcid: 3614514
Borissova AM, Djambazova A, Todorov K et al (1993) Effect of erythropoietin on the metabolic state and peripheral insulin sensitivity in diabetic patients on haemodialysis. Nephrol Dial Transplant 8:93. https://doi.org/10.1093/oxfordjournals.ndt.a092282
doi: 10.1093/oxfordjournals.ndt.a092282 pubmed: 8381946
Arcasoy MO (2008) The non-haematopoietic biological effects of erythropoietin. Br J Haematol 141:14–31. https://doi.org/10.1111/j.1365-2141.2008.07014.x
doi: 10.1111/j.1365-2141.2008.07014.x pubmed: 18324962
Teng R, Gavrilova O, Suzuki N et al (2011) Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production. Nat Commun 2:520. https://doi.org/10.1038/ncomms1526
doi: 10.1038/ncomms1526 pubmed: 22044999
Alnaeeli M, Raaka BM, Gavrilova O et al (2014) Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity. Diabetes 63:2415–2431. https://doi.org/10.2337/db13-0883
doi: 10.2337/db13-0883 pubmed: 24647735 pmcid: 4066343
Wang L, Teng R, Di L et al (2013) PPARα and Sirt1 mediate erythropoietin action in increasing metabolic activity and browning of white adipocytes to protect against obesity and metabolic disorders. Diabetes 62:4122–4131. https://doi.org/10.2337/db13-0518
doi: 10.2337/db13-0518 pubmed: 23990359 pmcid: 3837041
Caillaud C, Mechta M, Ainge H et al (2015) Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats. J Endocrinol 225:77–88. https://doi.org/10.1530/JOE-15-0010
doi: 10.1530/JOE-15-0010 pubmed: 25767056
Kodo K, Sugimoto S, Nakajima H et al (2017) Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice. PLoS ONE 12(3):e0173661. https://doi.org/10.1371/journal.pone.0173661
doi: 10.1371/journal.pone.0173661 pubmed: 28288167 pmcid: 5348037
Lee J, Walter MF, Korach KS, Noguchi CT (2021) Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha. Mol Metab 45:101142. https://doi.org/10.1016/j.molmet.2020.101142
doi: 10.1016/j.molmet.2020.101142 pubmed: 33309599
Przybyszewska J, Żekanowska E, Kędziora-Kornatowska K et al (2013) Comparison of serum prohepcidin and iron metabolism parameters in obese and non-obese elderly individuals. Endokrynol Pol 64:272–277. https://doi.org/10.5603/ep.2013.0005
doi: 10.5603/ep.2013.0005 pubmed: 24002954
Hämäläinen P, Saltevo J, Kautiainen H et al (2012) Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study. Cardiovasc Diabetol 11:116. https://doi.org/10.1186/1475-2840-11-116
doi: 10.1186/1475-2840-11-116 pubmed: 23016887 pmcid: 3471017
Sano M, Goto S (2019) Possible mechanism of hematocrit elevation by sodium glucose cotransporter 2 inhibitors and associated beneficial renal and cardiovascular effects. Circulation 139:1985–1987. https://doi.org/10.1161/CIRCULATIONAHA.118.038881
doi: 10.1161/CIRCULATIONAHA.118.038881 pubmed: 31009585
Pereira MJ, Eriksson JW (2019) Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs 79:219–230. https://doi.org/10.1007/s40265-019-1057-0
doi: 10.1007/s40265-019-1057-0 pubmed: 30701480 pmcid: 6394798
Lauritsen KM, Søndergaard E, Svart M et al (2018) Ketone body infusion increases circulating erythropoietin and bone marrow glucose uptake. Diabetes Care 41:e152–e154. https://doi.org/10.2337/dc18-1421
doi: 10.2337/dc18-1421 pubmed: 30327354
Kimita W, Bharmal SH, Ko J et al (2021) Effect of β-hydroxybutyrate monoester on markers of iron metabolism in new-onset prediabetes: findings from a randomised placebo-controlled trial. Food Funct 12:9229–9237. https://doi.org/10.1039/d1fo00729g
doi: 10.1039/d1fo00729g pubmed: 34606529
Voss JD, Allison DB, Webber BJ et al (2014) Lower obesity rate during residence at high altitude among a military population with frequent migration: a quasi experimental model for investigating spatial causation. PLoS ONE 9:e93493. https://doi.org/10.1371/journal.pone.0093493
doi: 10.1371/journal.pone.0093493 pubmed: 24740173 pmcid: 3989193
Petousi N, Croft QPP, Cavalleri GL et al (1985) (2014) Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia. J Appl Physiol 116:893–904. https://doi.org/10.1152/japplphysiol.00535.2013
doi: 10.1152/japplphysiol.00535.2013
Gomez-Arbelaez D, Bellido D, Castro AI et al (2017) Body composition changes after very-low-calorie ketogenic diet in obesity evaluated by 3 standardized methods. J Clin Endocrinol Metab 102:488–498. https://doi.org/10.1210/jc.2016-2385
doi: 10.1210/jc.2016-2385 pubmed: 27754807
Sajoux I, Lorenzo PM, Gomez-Arbelaez D et al (2019) Effect of a very-low-calorie ketogenic diet on circulating myokine levels compared with the effect of bariatric surgery or a low-calorie diet in patients with obesity. Nutrients 11:2368. https://doi.org/10.3390/nu11102368
doi: 10.3390/nu11102368 pubmed: 31590286 pmcid: 6835835
Lorenzo PM, Sajoux I, Izquierdo AG et al (2022) Immunomodulatory effect of a very-low-calorie ketogenic diet compared with bariatric surgery and a low-calorie diet in patients with excessive body weight. Clin Nutr 41:1566–1577. https://doi.org/10.1016/j.clnu.2022.05.007
doi: 10.1016/j.clnu.2022.05.007 pubmed: 35667273
Muscogiuri G, El Ghoch M, Colao A et al (2021) European guidelines for obesity management in adults with a very low-calorie ketogenic diet: a systematic review and meta-analysis. Obes Facts 14:222–245. https://doi.org/10.1159/000515381
doi: 10.1159/000515381 pubmed: 33882506 pmcid: 8138199
Caprio M, Infante M, Moriconi E et al (2019) Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE). J Endocrinol Invest 42:1365–1386. https://doi.org/10.1007/s40618-019-01061-2
doi: 10.1007/s40618-019-01061-2 pubmed: 31111407
de Luis D, Domingo JC, Izaola O et al (2016) Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial. Endocrine 54:111–122. https://doi.org/10.1007/s12020-016-0964-z
doi: 10.1007/s12020-016-0964-z pubmed: 27117144
Moreno B, Bellido D, Sajoux I et al (2014) Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine 47:793–805. https://doi.org/10.1007/s12020-014-0192-3
doi: 10.1007/s12020-014-0192-3 pubmed: 24584583
Moreno B, Crujeiras AB, Bellido D et al (2016) Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease. Endocrine 54:681–690. https://doi.org/10.1007/s12020-016-1050-2
doi: 10.1007/s12020-016-1050-2 pubmed: 27623967
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2015) Scientific Opinion on the essential composition of total diet replacements for weight control. EFSA J 13(1):3957. https://doi.org/10.2903/j.efsa.2015.3957
Heber D, Greenway FL, Kaplan LM et al (2010) Endocrine and nutritional management of the post-bariatric surgery patient: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 95:4823–4843. https://doi.org/10.1210/jc.2009-2128
doi: 10.1210/jc.2009-2128 pubmed: 21051578
Brolin RE, Gorman RC, Milgrim LM, Kenler HA (1991) Multivitamin prophylaxis in prevention of post-gastric bypass vitamin and mineral deficiencies. Int J Obes 15:661–667
pubmed: 1752727
Yanoff LB, Menzie CM, Denkinger B et al (2007) Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes (Lond) 31:1412–1419. https://doi.org/10.1038/sj.ijo.0803625
doi: 10.1038/sj.ijo.0803625 pubmed: 17438557
Lago F, Dieguez C, Gómez-Reino J, Gualillo O (2007) Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 3:716–724. https://doi.org/10.1038/ncprheum0674
doi: 10.1038/ncprheum0674 pubmed: 18037931
Ma W, Jia L, Xiong Q et al (2021) The role of iron homeostasis in adipocyte metabolism. Food Funct 12:4246–4253. https://doi.org/10.1039/d0fo03442h
doi: 10.1039/d0fo03442h pubmed: 33876811
Tussing-Humphreys LM, Nemeth E, Fantuzzi G et al (2010) Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring) 18:1449–1456. https://doi.org/10.1038/oby.2009.319
doi: 10.1038/oby.2009.319 pubmed: 19816411
Skikne BS, Flowers CH, Cook JD (1990) Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 75:1870–1876
doi: 10.1182/blood.V75.9.1870.1870 pubmed: 2331526
Ahluwalia N, Skikne BS, Savin V, Chonko A (1997) Markers of masked iron deficiency and effectiveness of EPO therapy in chronic renal failure. Am J Kidney Dis 30:532–541. https://doi.org/10.1016/s0272-6386(97)90313-9
doi: 10.1016/s0272-6386(97)90313-9 pubmed: 9328369
Gaborit B, Ancel P, Abdullah AE et al (2021) Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study. Cardiovasc Diabetol 20:57. https://doi.org/10.1186/s12933-021-01237-2
doi: 10.1186/s12933-021-01237-2 pubmed: 33648515 pmcid: 7919089
Paoli A, Cenci L, Pompei P et al (2021) Effects of two months of very low carbohydrate ketogenic diet on body composition, muscle strength, muscle area, and blood parameters in competitive natural body builders. Nutrients 13:374. https://doi.org/10.3390/nu13020374
doi: 10.3390/nu13020374 pubmed: 33530512 pmcid: 7911670
Dey S, Lee J, Noguchi CT (2021) Erythropoietin non-hematopoietic tissue response and regulation of metabolism during diet induced obesity. Front Pharmacol 12:725734. https://doi.org/10.3389/fphar.2021.725734
doi: 10.3389/fphar.2021.725734 pubmed: 34603036 pmcid: 8479821
Barrea L, Caprio M, Watanabe M et al (2022) Could very low-calorie ketogenic diets turn off low grade inflammation in obesity? Emerging evidence. Crit Rev Food Sci Nutr 12(3):1–17. https://doi.org/10.1080/10408398.2022.2054935
doi: 10.1080/10408398.2022.2054935
Crujeiras AB, Gomez-Arbelaez D, Zulet MA et al (2017) Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress? Int J Obes 41:1570–1578. https://doi.org/10.1038/ijo.2017.138
doi: 10.1038/ijo.2017.138
Crujeiras AB, Zulet MA, Lopez-Legarrea P et al (2014) Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients. Metabolism 63:520–531. https://doi.org/10.1016/j.metabol.2013.12.007
doi: 10.1016/j.metabol.2013.12.007 pubmed: 24439241
Crujeiras AB, Zulet MA, Abete I et al (2016) Interplay of atherogenic factors, protein intake and betatrophin levels in obese-metabolic syndrome patients treated with hypocaloric diets. Int J Obes (Lond) 40:403–410. https://doi.org/10.1038/ijo.2015.206
doi: 10.1038/ijo.2015.206 pubmed: 26443337
Crujeiras AB, Goyenechea E, Abete I et al (2010) Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab 95:5037–5044. https://doi.org/10.1210/jc.2009-2566
doi: 10.1210/jc.2009-2566 pubmed: 20719836
Crujeiras AB, Izquierdo AG, Primo D et al (2021) Epigenetic landscape in blood leukocytes following ketosis and weight loss induced by a very low calorie ketogenic diet (VLCKD) in patients with obesity. Clin Nutr 40:3959–3972. https://doi.org/10.1016/j.clnu.2021.05.010
doi: 10.1016/j.clnu.2021.05.010 pubmed: 34139469
Wang L, Di L, Noguchi CT (2014) AMPK is involved in mediation of erythropoietin influence on metabolic activity and reactive oxygen species production in white adipocytes. Int J Biochem Cell Biol 54:1–9. https://doi.org/10.1016/j.biocel.2014.06.008
doi: 10.1016/j.biocel.2014.06.008 pubmed: 24953559 pmcid: 4160370
Tozzi R, Cipriani F, Masi D et al (2022) Ketone bodies and SIRT1, synergic epigenetic regulators for metabolic health: a narrative review. Nutrients. https://doi.org/10.3390/nu14153145
doi: 10.3390/nu14153145 pubmed: 35956321 pmcid: 9370141

Auteurs

A Fernandez-Pombo (A)

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Travesía da Choupana Street s/n, 15706, Santiago de Compostela, La Coruna, Spain.
Endocrinology and Nutrition Division, Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.

P M Lorenzo (PM)

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Travesía da Choupana Street s/n, 15706, Santiago de Compostela, La Coruna, Spain.
CIBER Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Madrid, Spain.

M C Carreira (MC)

CIBER Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Madrid, Spain.
Molecular Endocrinology Group, Instituto de Investigacion Sanitaria de Santiago de Com-Postela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.

D Gomez-Arbelaez (D)

Faculty of Health Sciences, University of Santander (UDES), Bucaramanga, Colombia.

A I Castro (AI)

CIBER Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Madrid, Spain.
Molecular Endocrinology Group, Instituto de Investigacion Sanitaria de Santiago de Com-Postela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.

D Primo (D)

Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Investigation, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain.

J Rodriguez (J)

Clinical Biochemistry Laboratory, Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.

I Sajoux (I)

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Travesía da Choupana Street s/n, 15706, Santiago de Compostela, La Coruna, Spain.
Medical Department Pronokal Group, Barcelona, Spain.

J Baltar (J)

Division of General Surgery, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.

D de Luis (D)

Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Investigation, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain.

D Bellido (D)

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Travesía da Choupana Street s/n, 15706, Santiago de Compostela, La Coruna, Spain.
Endocrinology and Nutrition Unit, Complejo Hospitalario Universitario de Ferrol (CHUF/SERGAS), Ferrol, Spain.

A B Crujeiras (AB)

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Travesía da Choupana Street s/n, 15706, Santiago de Compostela, La Coruna, Spain. anabelencrujeiras@hotmail.com.
CIBER Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Madrid, Spain. anabelencrujeiras@hotmail.com.
ORCID: 0000-0003-4392-0301

F F Casanueva (FF)

CIBER Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Madrid, Spain.
Molecular Endocrinology Group, Instituto de Investigacion Sanitaria de Santiago de Com-Postela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.

Classifications MeSH