Revista Colombiana de Ciencias Químico-Farmacéuticas

(1) M. Ng, Ch. J.L. Murray, "Nearly one-third of the world’s population is obese

or overweight, new data show", Institute for Health Metrics and Evaluation

(IHME) at the University of Washington, Seattle, USA, 2014.

(2) The GBD 2015 Obesity Collaborators, Health Effects of Overweight and Obesity

in 195 Countries over 25 Years, The New England Journal of Medicine, 1-15 (2017).

(3) C.F. Fernandez, El 30 por ciento de la poblacion mundial tiene exceso de peso, El

Tiempo, Bogota-Colombia, 2017.

(4) WHO, Prevalence of overweight & obesity map. En: "Stop the global epidemic

of chronic disease", edit. por World Health Organization, Geneva, 2010.

(5) J. Rivera-Dommarco, J.P. Gutierrez, T. Shamah-Levy, S. Villalpando-Hernandez,

A. Franco, L. Cuevas-Nasu, et al., "Encuesta Nacional de Salud y Nutricion

Resultados Nacionales", Instituto Nacional de Salud Publica, Cuernavaca,

Mexico, 2012.

(6) S.D. Stovitz, P.J. Hannan, L.A. Lytle, E.W. Demerath, M.A. Pereira, J.H. Himes,

Child height and the risk of young-adult obesity, American Journal of Preventive

Medicine, 38 (1), 74 (2010).

(7) A. Anandacoomarasamy, I. Caterson, P. Sambrook, M. Fransen, L. March, The

impact of obesity on the musculoskeletal system, Int. J. Obes. (Lond), 32(2), 211-

(2008).

(8) A. Anandacoomarasamy, M. Fransen, L. March, Obesity and the musculoskeletal

system, Curr. Opin. Rheumatol., 21(1), 71-77 (2009).

(9) G. Espejo, Minsalud revelo preocupante panorama por obesidad y sobrepeso en

Colombia, El Espectador, Bogota-Colombia, 2015.

(10) OMS (Organizacion Mundial de la Salud), "Datos y cifras sobre obesidad infantil",

OMS, Ginebra, Suiza, 2016.

(11) M.K. Badman, J.S. Flier, The gut and energy balance: visceral allies in the obesity

wars, Science, 307(5717), 1909-1914 (2005).

(12) R.F. Witkamp, Current and future drug targets in weight management, Pharmaceutical

Research, 28(8), 1792-1818 (2010).

(13) C.P. Cannon, A. Kumar, Treatment of overweight and obesity: lifestyle, pharmacologic,

and surgical options, Clin. Cornerstone, 9(4), 55-68, discussion 69-71

(2009); Y. Wang, M.A. Beydoun, The obesity epidemic in the United States-

-gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic

review and meta-regression analysis, Epidemiol. Rev., 29, 6-28 (2007).

(14) J.D. Roth, B.L. Roland, R.L. Cole, J.L. Trevaskis, C. Weyer, J.E. Koda, et al.,

Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence

from nonclinical and clinical studies, Proc. Natl. Acad. Sci. USA, 105(20),

-7262 (2008).

(15) O. Chaudhri, C. Small, S. Bloom, Gastrointestinal hormones regulating appetite,

Philos. Trans. R. Soc. Lond. B, Biol. Sci., 361(1471), 1187-1209 (2006).

(16) J.H. Yu, M.S. Kim, Molecular mechanisms of appetite regulation, Diabetes

Metab. J., 36(6), 391-398 (2012).

(17) E. Maratos-Flier, J.S. Flier, What fuels fat., Sci. Am., 297(3), 72-81 (2007).

(18) V. Salem, S.R Bloom, Approaches to the pharmacological treatment of obesity,

Expert Rev. Clin. Pharmacol., 3(1), 73-88 (2010).

(19) J. Gibbs, R.C. Young, G.P. Smith, Cholecystokinin decreases food intake in rats,

J. Comp. Physiol. Psychol., 84(3), 488-495 (1973).

(20) M. Londono, L.A. Tellez, R. Gutierrez, Physiological low doses of leptin and

cholecystokinin induces body weight-loss in juvenile and lean, but not in adultobese

rats, Letters in Peptide Science, 18(1), 77-88 (2012).

(21) J.C. Halford, E.J. Boyland, J.E. Blundell, T.C. Kirkham, J.A. Harrold, Pharmacological

management of appetite expression in obesity, Nat. Rev. Endocrinol.,

(5), 255-269 (2010).

(22) P.C. Konturek, J.W. Konturek, M. Czesnikiewicz-Guzik, T. Brzozowski, E. Sito,

et al., Neuro-hormonal control of food intake: basic mechanisms and clinical

implications, J. Physiol. Pharmacol., 56 Suppl 6, 5-25 (2005).

(23) Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, J.M. Friedman, Positional

cloning of the mouse obese gene and its human homologue, Nature, 372(6505),

(1994).

(24) L.A. Campfield, F.J. Smith, Y. Guisez, R. Devos, P. Burn, Recombinant mouse

OB protein: evidence for a peripheral signal linking adiposity and central neural

networks, Science, 269(5223), 546-549 (1995); J.L. Halaas, K.S. Gajiwala, M.

Maffei, S.L.

(25) Cohen, B.T. Chait, D. Rabinowitz, et al., Weight-reducing effects of the plasma

protein encoded by the obese gene, Science, 269(5223), 543-546 (1995); M.A.

Pelleymounter, M.J. Cullen, M.B. Baker, R. Hecht, D. Winters, T. Boone, et al.,

Effects of the obese gene product on body weight regulation in ob/ob mice, Science,

(5223), 540-543 (1995); T.W. Stephens, M. Basinski, P.K. Bristow, J.

M. Bue-Valleskey, S.G. Burgett, et al., The role of neuropeptide Y in the antiobesity

action of the obese gene product, Nature, 377 (6549), 530-532 (1995); D.S.

Weigle, T.R. Bukowski, D.C. Foster, S.

(26) Holderman, J.M. Kramer, G. Lasser, et al., Recombinant ob protein reduces

feeding and body weight in the ob/ob mouse, J. Clin. Invest., 96(4), 2065-2070

(1995).

(27) G.J. Morton, D.E. Cummings, D.G. Baskin, G.S. Barsh, M.W. Schwartz, Central

nervous system control of food intake and body weight, Nature, 443 (7109),

-295 (2006).

(28) F. Zhang, M.B. Basinski, J.M. Beals, S.L. Briggs, L.M. Churgay, D.K. Clawson, et

al., Crystal structure of the obese protein leptin-E100, Nature, 387(6629), 206-

(1997).

(29) M.W. Schwartz, R.J. Seeley, L.A. Campfield, P. Burn, D.G. Baskin, Identification

of targets of leptin action in rat hypothalamus, J. Clin. Invest., 98(5), 1101-1106

(1996).

(30) J.L. Halaas, J.M. Friedman, Leptin and the regulation of body weight in mammals,

Nature, 395(6704), 763-770 (1998 ).

(31) M.E. Gearing, The “skinny” on Celastrol, a potential future anti-obesity drug, Science

in the News, Blog, 2015, URL: http://sitn.hms.harvard.edu/flash/2015/

the-skinny-on-celastrol-a-potential-future-anti-obesity-drug/, consultado el 30

de agosto de 2016.

(32) S. Cinti, R.D. Matteis, C. Pico, E. Ceresi, A. Obrador, C. Maffeis, et al., Secretory

granules of endocrine and chief cells of human stomach mucosa contain

leptin, Int. J. Obes. Relat. Metab. Disord., 24(6), 789-793 (2000); I. Sobhani, A.

Bado, C.

(33) Vissuzaine, M. Buyse, S. Kermorgant, J.P. Laigneau, et al., Leptin secretion and

leptin receptor in the human stomach, Gut, 47(2), 178-183 (2000).

(34) A. Bado, S. Levasseur, S. Attoub, S. Kermorgant, J.P. Laigneau, M.N. Bortoluzzi,

et al., The stomach is a source of leptin, Nature, 394(6695), 790-793 (1998).

(35) Anubhuti, S. Arora, Leptin and its metabolic interactions: an update, Diabetes

Obes. Metab., 10(11), 973-993 (2008).

(36) U. Meier, A.M. Gressner, Endocrine regulation of energy metabolism: review of

pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin,

and resistin, Clin. Chem., 50(9), 1511 (2004).

(37) G. Hervieu, Melanin-concentrating hormone functions in the nervous system:

food intake and stress, Expert Opin. Ther. Targets, 7(4), 495-511 (2003).

(38) A. Yamanaka, C.T. Beuckmann, J.T. Willie, J. Hara, N. Tsujino, M. Mieda, et al.,

Hypothalamic orexin neurons regulate arousal according to energy balance in

mice, Neuron, 38(5), 701-713 (2003).

(39) H. Dumond, N. Presle, B. Terlain, D. Mainard, D. Loeuille, P. Netter, et al., Evidence

for a key role of leptin in osteoarthritis, Arthritis Rheum., 48(11), 3118-

(2003).

(40) J. Kozakowsk, Obesity and musculoskeletal system, Postępy Nauk Medycznych,

XXIX(12), 910 (2016).

(41) D. Azamar-Llamas, G. Hernandez-Molina, B. Ramos-Avalos, J. Furuzawa-Carballeda,

Adipokine contribution to the pathogenesis of osteoarthritis, Mediators

Inflamm., 2017, 5468023 (2017).

(42) S. Rossner, M. Hammarstrand, E. Hemmingsson, M. Neovius, K. Johansson,

Long-term weight loss and weight-loss maintenance strategies, Obes. Rev., 9(6),

-630 (2008); J.M. Jakicic, The effect of physical activity on body weight, Obesity

(Silver Spring), 17 Suppl 3, S34-S38 (2009).

(43) M. Ravishankar Ram, G. Beena, P. Ragunathan, R. Malathi, Analysis of structure,

function, and evolutionary origin of the ob gene product-leptin, J. Biomol.

Struct. Dyn., 25 (2), 183-188 (2007).

(44) K.G. Murphy, S.R. Bloom, Gut hormones and the regulation of energy homeostasis,

Nature, 444(7121), 854-859 (2006); M.A. Beydoun, Y. Wang, The obesity

epidemic in the United States-gender, age, socioeconomic, racial/ethnic,

and geographic characteristics: a systematic review and meta-regression analysis,

Epidemiol. Rev., 29, 6-28 (2007).

(45) Endocrine Society, "Obesity Experts Recommend Weight Loss Drugs, Surgery

as Supplement to Lifestyle Interventions", Washington, DC, 2015.

(46) M. Tsai, A. Asakawa, H. Amitani, A. Inui, Stimulation of leptin secretion by

insulin, Indian J. Endocrinol. Metab., 16(Suppl 3), S543-S548 (2012).

(47) M.E. Londono-Lemos, Tratamiento farmacologico contra la obesidad, Rev. Colomb.

Cienc. Quím. Farm., 41(2), 217-261 (2012.).

(48) Raquel Cristina Lopes Assis Coelho, Anti-Obesity Drugs: A Necessary Part of

Treatment, J. Obes. W.-L. Med., 1:1 (2015).

(49) E. Colman, J. Golden, M. Roberts, A. Egan, J. Weaver, C. Rosebraugh, The

FDA's assessment of two drugs for chronic weight management, N. Engl. J. Med.,

(17), 1577-1579 (2012).

(50) M.D. Sarah Goodpastor, "Drug Therapy for Obesity: A “Magic” Little Pill?",

American Board of Obesity Medicine, Houston, Texas, 2015.

(51) D.L. Coleman, Obese and diabetes: two mutant genes causing diabetes-obesity

syndromes in mice, Diabetologia, 14(3), 141-148 (1978).

(52) A. Palou, M.L. Bonet, C. Pico, A.M. Rodriguez, [Nutrigenomics and obesity],

Rev. Med. Univ. Navarra, 48(2), 36-48 (2004).

(53) L.K. Heisler, M.A. Cowley, T. Kishi, L.H. Tecott, W. Fan, M.J. Low, et al., Central

serotonin and melanocortin pathways regulating energy homeostasis, Ann.

N. Y. Acad. Sci., 994, 169-174 (2003).

(54) P. Rogers, P.E. McKibbin, G. Williams, Acute fenfluramine administration

reduces neuropeptide Y concentrations in specific hypothalamic regions of the

rat: possible implications for the anorectic effect of fenfluramine, Peptides, 12(2),

-255 (1991).

(55) C.M. Brown, D.V. Coscina, Ineffectiveness of hypothalamic serotonin to block

neuropeptide Y-induced feeding, Pharmacol. Biochem. Behav., 51(4), 641-646

(1995).

(56) A.S. Garfield, L. K. Heisler, Pharmacological targeting of the serotonergic system

for the treatment of obesity, J. Physiol., 587(Pt 1), 49-60 (2009).

(57) F.L. Greenway, G.A. Bray, Combination drugs for treating obesity, Curr. Diab.

Rep., 10(2), 108-115 (2010).

(58) R.D. Hurt, D.P. Sachs, E.D. Glover, K.P. Offord, J.A. Johnston, L.C. Dale, et al.,

A comparison of sustained-release bupropion and placebo for smoking cessation,

T. N. Eng. J. Med., 337(17), 1195-1202 (1997).

(59) J.S. MacDaniels, T.L. Schwartz, Effectiveness, tolerability and practical application

of the newer generation anti-obesity medications, Drugs Context, 5, 212291

(2016).

(60) S.L. McElroy, A.I. Guerdjikova, D.D. Kim, C. Burns, R. Harris-Collazo, R.

Landbloom, et al., Naltrexone/Bupropion combination therapy in overweight

or obese patients with major depressive disorder: results of a pilot study, Prim.

Care Companion CNS Disord., 15(3) (2013).

(61) C.F. Elias, C. Aschkenasi, C. Lee, J. Kelly, R.S. Ahima, C. Bjorbaek, et al., Leptin

differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic

area, Neuron, 23(4), 775-786 (1999).

(62) L. De Marinis, A. Mancini, D. Valle, A. Bianchi, A.M. De Luca, A.M. Fulghesu,

et al., Influence of chronic Naltrexone treatment on growth hormone and insulin

secretion in obese subjects, Int. J. Obes. Relat. Metab. Disord., 21(11), 1076-1081

(1997).

(63) D.B. Samadi, All you need to know about Qsymia, Fox News, New York, USA,

(64) R. Eckel, Pharmacotherapy for Obesity: Filling a Therapeutic Gap, Am. J. Manag.

Car. 2013, URL: http://www.ajmc.com/conferences/ada-2013/pharmacotherapy-

for-obesity-filling-a-therapeutic-gap, consultado el 30 de agosto de 2016.

(65) FDA Endocrinologic and Metabolic Drugs Advisory Committee, "FDA briefing

document NDA 206231 liraglutide injection 3 mg tablets 10 mg", Food and

Drug Administration, Washington, DC, 2014.

(66) European Medicines Agency, "Liraglutide (Saxenda) EPAR Product Information",

European public assessment reports, London, 2015.

(67) D.L. Williams, D.G. Baskin, M.W. Schwartz, Leptin regulation of the anorexic

response to glucagon-like peptide-1 receptor stimulation, Diabetes, 55(12), 3387-

(2006).

(68) C. Clemmensen, J. Chabenne, B. Finan, L. Sullivan, K. Fischer, D. Kuchler, et al.,

GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically

maintained on an obesogenic diet, Diabetes, 63(4), 1422-1427 (2014).

(69) T.D. Muller, L.M. Sullivan, K. Habegger, C. X. Yi, D. Kabra, E. Grant, et al., Restoration

of leptin responsiveness in diet-induced obese mice using an optimized

leptin analog in combination with exendin-4 or FGF21, J. Pept. Sci., 18(6), 383-

(2012).

(70) E.E. Ladenheim, Liraglutide and obesity: a review of the data so far, Drug Des.

Devel. Ther., 9, 1867-1875 (2015).

(71) E.W. Iepsen, J. Lundgren, C. Dirksen, J.E. Jensen, O. Pedersen, T. Hansen, et al.,

Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma

leptin during maintenance of weight loss, Int. J. Obes. (Lond), 39(5), 834-841

(2015).

(72) S. Moschos, G. Matarese, C.S. Mantzoros, Leptin in immunology, J. Immunol.,

(6), 3137-3142 (2005).

(73) S.J. Guyenet, M.W. Schwartz, Clinical review: Regulation of food intake, energy

balance, and body fat mass: implications for the pathogenesis and treatment of

obesity, J. Clin. Endocrinol. Metab., 97(3), 745-755 (2012).

(74) Ch.-X. Yi, J.P. Thaler, E.A. Schur, S.J. Guyenet, B.H. Hwang, et al., Obesity is

associated with hypothalamic injury in rodents and humans, J. Clin. Inv., 122(1),

-162 (2012).

(75) J.P. Thaler, S.J. Guyenet, M.D. Dorfman, B.E. Wisse, M.W. Schwartz, Hypothalamic

inflammation: marker or mechanism of obesity pathogenesis?, Diabetes,

(8), 2629 (2013).

(76) P.J. Enriori, A.E. Evans, P. Sinnayah, E.E. Jobst, L. Tonelli-Lemos, S.K. Billes, et

al., Diet-induced obesity causes severe but reversible leptin resistance in arcuate

melanocortin neurons, Cell. Metab., 5(3), 181-194 (2007).

(77) K. El-Haschimi, D.D. Pierroz, S.M. Hileman, C. Bjorbaek, J.S. Flier, Two defects

contribute to hypothalamic leptin resistance in mice with diet-induced obesity,

J. Clin. Invest., 105(12), 1827-1832 (2000).

(78) W.H. Stearns, S.H. Bates, T.A. Dundon, M. Schubert, A.W. Tso, Y. Wang, et

al., STAT3 signalling is required for leptin regulation of energy balance but not

reproduction, Nature, 421(6925), 856-859 (2003).

(79) A. Barateiro, I. Mahu, A.I. Domingos, Leptin resistance and the neuro-adipose

connection, Front. Endocrinol. (Lausanne), 8, 45 (2017).

(80) H. Ghanim, S. Abuaysheh, C.L. Sia, K. Korzeniewski, A. Chaudhuri, J.M. Fernandez-

Real, et al., Increase in plasma endotoxin concentrations and the expression

of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear

cells after a high-fat, high-carbohydrate meal: implications for insulin resistance,

Diabetes Care, 32(12), 2281-2287 (2009).

(81) J. Salas-Salvado, X. Farres, X. Luque, S. Narejos, M. Borrell, J. Basora, et al., Effect of

two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight

or obese patients: a randomised trial, Br. J. Nutr., 99(6), 1380-1387 (2008).

(82) J.E. Reseland, S.A. Anderssen, K. Solvoll, I. Hjermann, P. Urdal, I. Holme, et al.,

Effect of long-term changes in diet and exercise on plasma leptin concentrations,

Am. J. Clin. Nutr., 73(2), 240-245 (2001).

(83) K. Spiegel, R. Leproult, M. L'Hermite-Baleriaux, G. Copinschi, P.D. Penev, E.

Van Cauter, Leptin levels are dependent on sleep duration: relationships with

sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin, J.

Clin. Endocrinol. Metab., 89(11), 5762-5771 (2004).

(84) A.B. Coon, W.A. Banks, S.M. Robinson, A. Moinuddin, J.M. Shultz, R. Nakaoke,

et al., Triglycerides induce leptin resistance at the blood-brain barrier, Diabetes,

(5), 1253-1260 (2004).

(85) N. Iqbal, F.F. Samaha, P. Seshadr, K.L. Chicano, D.A. Daily, J. McGrory, et al.,

A low-carbohydrate as compared with a low-fat diet in severe obesity, N. Eng. J.

Med., 348(21), 2074-2081 (2003).

(86) D.S. Weigle, P.A. Breen, C.C. Matthys, H.S. Callahan, K.E. Meeuws, V.R.

Burden, et al., 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., 82(1), 41-48

(2005).

(87) H. Pan, J. Guo, Z. Su, Advances in understanding the interrelations between

leptin resistance and obesity, Physiol. Behav., 130, 157-169 (2014).

(88) G.T. Dodd, S. Decherf, K. Loh, S.E. Simonds, F. Wiede, E. Balland, et al., Leptin

and insulin act on POMC neurons to promote the browning of white fat, Cell,

(1-2), 88-104 (2015).

(89) G. Boden, Endoplasmic reticulum stress: another link between obesity and insulin

resistance/inflammation?, Diabetes, 58(3), 518-519 (2009).

(90) G. Aubert, V. Mansuy, M.J. Voirol, L. Pellerin, F.P. Pralong, The anorexigenic

effects of metformin involve increases in hypothalamic leptin receptor expression,

Metabolism, 60(3), 327-334 (2011).

(91) Y.W. Kim, J.Y. Kim, Y.H. Park, S.Y. Park, K.C. Won, K.H. Choi, et al., Metformin

restores leptin sensitivity in high-fat-fed obese rats with leptin resistance,

Diabetes, 55(3), 716-724 (2006).

(92) K.B. Alexandre, A.M. Smit, I.P. Gray, N.J. Crowther, Metformin inhibits intracellular

lipid accumulation in the murine pre-adipocyte cell line, 3T3-L1, Diabetes

Obes. Metab., 10(8), 688-690 (2008).

(93) National Health Service-NHS, "Treating obesity ", London-England, 2016.

(94) M. Sahin, N. Tanaci, M. Yucel, M. Kutlu, N.B. Tutuncu, B. Pamuk, et al., Acute

effects of orlistat on postprandial serum leptin levels in nondiabetic obese

patients, Minerva Endocrinol., 33(3), 169-173 (2008).

(95) Y. Ozkan, S. Aydin, E. Donder, S.S. Koca, B. Ozkan, I. Sahin, Effect of orlistat

on the total ghrelin and leptin levels in obese patients, J. Physiol. Biochem., 65(3),

-223 (2009).

(96) A.R. Barrios, R. Rey, El efecto pleiotropico es primordial para el beneficio del

tratamiento con estatinas, Rev. Arg. Cardiol.., 75(1), 42-47 (2007).

(97) D. Dimitrov, H. Bohchelian, L. Koeva, Effect of orlistat on plasma leptin levels

and risk factors for the metabolic syndrome, Metab. Syndr. Relat. Disord., 3(2),

-129 (2005).

(98) J.W. Yun, Possible anti-obesity therapeutics from nature--a review, Phytochemistry,

(14-15), 1625-1641 (2010).

(99) M. Rosenbaum, R. Goldsmith, D. Bloomfield, A. Magnano, L. Weimer, S.

Heymsfield, et al., Low-dose leptin reverses skeletal muscle, autonomic, and

neuroendocrine adaptations to maintenance of reduced weight, J. Clin. Invest.,

(12), 3579-3586 (2005); M. Rosenbaum, M. Sy, K. Pavlovich, R.L. Leibel, J.

Hirsch, Leptin reverses weight loss-induced changes in regional neural activity

responses to visual food stimuli, J. Clin. Invest., 118(7), 2583-2591 (2008); K.M.

Baldwin, D.R. Joanisse, F. Haddad, R.L. Goldsmith, D. Gallagher, K.H. Pavlovich,

et al., Effects of weight loss and leptin on skeletal muscle in human subjects,

Am. J. Physiol. Regul. Integr. Comp. Physiol., 301(5), R1259-R1266 (2011).

(100) R. Sherafat-Kazemzadeh, S.Z. Yanovski, J.A. Yanovski, Pharmacotherapy for

childhood obesity: present and future prospects, Int. J. Obes. (Lond), 37(1), 1-15

(2013).

(101) D.J. Clegg, S.C. Benoit, R.J. Seeley, S.C. Woods, Insulin and leptin as adiposity

signals, Recent Progress in Hormone Research, 59, 267-285 (2004).

(102) E.L. Air, S.C. Benoit, D.J. Clegg, R.J. Seeley, S.C. Woods, Insulin and leptin

combine additively to reduce food intake and body weight in rats, Endocrinology,

(6), 2449-2452 (2002).

(103) S.C. Benoit, D.J. Clegg, R.J. Seeley, S.C. Woods, Insulin and leptin as adiposity

signals, Recent Progr. Horm. Res., 59, 267-285 (2004).

(104) A. Hamidi, H. Fakhrzadeh, A. Moayyeri, R. Heshmat, P. Ebrahimpour, B. Larijani,

Metabolic syndrome and leptin concentrations in obese children, Indian J.

Pediatr., 73(7), 593-596 (2006).

(105) D.A. Sarruf, J.P. Thaler, G.J. Morton, J. German, J.D. Fischer, K. Ogimoto, et al.,

Fibroblast growth factor 21 action in the brain increases energy expenditure and

insulin sensitivity in obese rats, Diabetes, 59(7), 1817-1824 (2010).

(106) T. Inagaki, P. Dutchak, G. Zhao, X. Ding, L. Gautron, V. Parameswara, et al.,

Endocrine regulation of the fasting response by PPARalpha-mediated induction

of fibroblast growth factor 21, Cell. Metab., 5(6), 415-425 (2007).

(107) B.J. Ko, S.M. Kim, K.H. Park, H.S. Park, C.S. Mantzoros, Levels of circulating

selenoprotein P, fibroblast growth factor (FGF) 21 and FGF23 in relation to the

metabolic syndrome in young children, Int. J. Obes. (Lond), 38(12), 1497-1502

(2014).

(108) L.R. Ibarra-Reynoso, L. Pisarchyk, E.L. Perez-Luque, M.E. Garay-Sevilla, J.

M. Malacara, Dietary restriction in obese children and its relation with eating

behavior, fibroblast growth factor 21 and leptin: a prospective clinical intervention

study, Nutr. Metab. (Lond), 12, 31 (2015).

(109) A.M. Goss, B.A. Gower, A lower-carbohydrate, higher-fat diet reduces abdominal

and intermuscular fat and increases insulin sensitivity in adults at risk of type

diabetes, J. Nutrition, 145(1), 177S-183S (2015 ).

(110) M.L. Armeno, A.G. Krochik, C.S. Mazza, Evaluation of two dietary treatments

in obese hyperinsulinemic adolescents, J. Pediatr. Endocrinol. Metab., 24(9-10),

-722 (2011).

(111) Y. Escalante, J.M. Saavedra, A. Garcia-Hermoso, A.M. Dominguez, Improvement

of the lipid profile with exercise in obese children: a systematic review,

Prev. Med., 54(5), 293-301 (2012).

(112) M. Plonka, A. Toton-Morys, P. Adamski, A. Suder, W. Bielanski, M.J. Dobrzanska,

A. Kaminska, B. Piorecka, J. Glodzik, Association of the physical activity

with leptin blood serum level, body mass indices and obesity in schoolgirls, J.

Physiol. Pharmacol., 62(6), 647-656 (2011).

(113) K. Karacabey, The effect of exercise on leptin, insulin, cortisol and lipid profiles

in obese children, J. Int. Med. Res., 37(5), 1472-1478 (2009).

(114) S.T. Paes, J.C. Marins, A.E. Andreazzi, [Metabolic effects of exercise on childhood

obesity: a current view], Rev. Paul. Pediatr., 33(1), 122-129 (2015).