Trayhurn P. Hypoxia and adipocyte physiology: implications
for adipose tissue dysfunction in obesity. Annu
Rev Nutr 2014;34:207-36. DOI: 10.1146/annurev-nutr-
-161156
Chaldakov GN, Fiore M, Hristova MG, Aloe L.
Metabotrophic potential of neurotrophins: implication in
obesity and related diseases? Med Sci Monit 2003; 9:HY19-
Chaldakov GN, Aloe L, Tonchev AB, Fiore M. From
Homo obesus to Homo diabesus: Neuroadipology insight.
In: Nóbrega C, Rodriguez-López R, (eds). Molecular
Mechanisms Underpinning the Development of Obesity,
Switzerland, Springer International Publishing, 2014; pp
-178.
Behl S, Singh J. Adipocytes under environmental assault:
Targets for obesity? In: Tappia PS et al (eds). Advances in
Biochemistry in Health and Disease, Volume 19, Switzerland,
Springer Nature 2020; pp 23-41.
Unamuno X, Gómez-Ambrosi J, Rodríguez A, Becerril
S, Frühbeck G, Catalán V. Adipokine dysregulation and adipose
tissue inflammation in human obesity. Eur J Clin
Invest 2018;48(9):e12997. DOI: 10.1111/eci.12997
Iacobellis G, Di Gioia C, Petramala L, et al. Brown fat expresses
adiponectin in humans. Int J Endocrinol 2013;
-126751.
Blirando K. Epigenetic Regulation of Adipocytes Phenotype:
Implication for Perivascular Adipose Tissue Contribution to
Cardiometabolic Diseases. Adipobiology 2016; 8:21-36.
Sacks H, Symonds ME. Anatomical locations of human
brown adipose tissue: functional relevance and implications
in obesity and type 2 diabetes. Diabetes 2013; 62(6):
-1790.
Villarroya F, Cereijo R, Villarroya J, et al. Toward an
Understanding of How Immune Cells Control Brown and
Beige Adipobiology. Cell Metabolism 2018;27(5): 954-961.
Levi-Montalcini R. The nerve growth factor 35 years later.
Science 1987;237(4819): 1154-1162.
Fiore M, Chaldakov GN, Aloe L. Nerve growth factor as a
signaling molecule for nerve cells and also for the neuroendocrine-
immune systems. Rev Neurosci 20(2): 133-145,
Aloe L, Tonchev A, Fiore M, Chaldakov G. Homo diabesus:
involvement of metabotrophic factors. Adipobiology
;5: 45-49.
Rocco ML, Soligo M, Manni L, Aloe L. Nerve Growth
Factor: Early Studies and Recent Clinical Trials. Curr
Neuropharmacol 2018;16(10): 1455-1465.
Aloe L, Levi-Montalcini R. Mast cells increase in tissues of
neonatal rats injected with the nerve growth factor. Brain
Res 1977;133(2): 358-366.
Chaldakov GN, Fiore M, Tonchev AB, et al. Homo obesus:
a metabotrophin-deficient species. Pharmacology and nutrition
insight. Curr Pharm Des 2007; 13(21): 2176-2179.
Chaldakov G. The metabotrophic NGF and BDNF: an
emerging concept. Arch Ital Biol 2011;149(2): 257-263.
Töre F, Tonchev A, Fiore M, et al. From Adipose Tissue
Protein Secretion to Adipopharmacology of Disease.
Immunol Endocr Metab Agents - Med Chem 2007; 7:149-
Yanev S, Aloe L, Fiore M, Chaldakov GN. Neurotrophic
and metabotrophic potential of nerve growth factor and
brain-derived neurotrophic factor: Linking cardiometabolic
and neuropsychiatric diseases. World J Pharmacol 2013;
(4): 92-99.
Rosenbaum T, Vidaltamayo R, Sánchez-Soto MC, et al.
Pancreatic beta cells synthesize and secrete nerve growth
factor. Proc Nat Acad Scien USA1998; 95(13): 7784-7788.
Vidaltamayo R, Mery C, Angeles-Angeles A, et al.
Expression of nerve growth factor in human pancreatic
beta cells. Growth Factors (Switzerland) 2003; 21:103-107.
Sornelli F, Fiore M, Chaldakov G, Aloe L. Brain-derived
neurotrophic factor: A new adipokine. Biomed Rev 2007;
:85-88.
Chaldakov GN, Fiore M, Stankulov IS, et al. Neurotrophin
presence in human coronary atherosclerosis and metabolic
syndrome: a role for NGF and BDNF in cardiovascular disease?
Prog Brain Res 2004;146:279-289.
Krabbe KS, Nielsen AR, Krogh-Madsen R, et al. Brainderived
neurotrophic factor (BDNF) and type 2 diabetes.
Diabetologia 2007;50(2): 431-438.
Yamanaka M, Itakura Y, Ono-Kishino M, et al. Intermittent
administration of brain-derived neurotrophic factor
(BDNF) ameliorates glucose metabolism and prevents
pancreatic exhaustion in diabetic mice. J Biosci Bioeng
;105(4): 395-402.
de la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes-
evidence reviewed. J Diabetes Sci Technol 2008;2(6):
-1113.
Dar TA, Sheikh IA, Ganie SA, et al. Molecular linkages between
diabetes and Alzheimer’s disease: current scenario
and future prospects. CNS Neurol Disord Drug Targets
;13(2): 290-298.
Sridhar GR, Thota H, Allam AR, et al. Alzheimer’s disease
and type 2 diabetes mellitus: the cholinesterase connection?
Lipids Health Dis 2006;5:28.
Aloe L, Tonchev AB, Maucher A, et al. Adipobiology of the
brain: From brain diabetes to adipose Alzheimer’s disease.
Adipobiology 2015;7:37-42.
Hristova M. NGF and BDNF in patients with metabolic
syndrome. Varna: Medical University; PhD Thesis. 2002.
Manni L, Nikolova V, Vyagova D, et al. Reduced plasma
levels of NGF and BDNF in patients with acute coronary
syndromes. Int J Cardiol 2005;102(1): 169-171.
Ejiri J, Inoue N, Kobayashi S, et al. Possible Role of Brain-
Derived Neurotrophic Factor in the Pathogenesis of
Coronary Artery Disease. Circulation 2005;112(14): 2114-
Sornelli F, Fiore M, Chaldakov GN, Aloe L. Adipose tissue-
derived nerve growth factor and brain-derived neurotrophic
factor: results from experimental stress and diabetes.
Gen Physiol Biophys 2009;28 Spec No 179-183.
Larrieta M, Vital P, Mendoza-Rodríguez A, et al. Nerve
growth factor increases in pancreatic beta cells after streptozotocin-
induced damage in rats. Exp Biol Med (Maywood,
N.J.) 2006;231:396-402.
Geroldi D, Minoretti P, Emanuele E. Brain-derived neurotrophic
factor and the metabolic syndrome: more than just
a hypothesis. Med Hypotheses 2006;67(1): 195-196.
Schulte-Herbrüggen O, Braun A, Wronski S, et al.
Neurotrophic Factors-A Tool for Therapeutic Strategies in
Neurological, Neuropsychiatric and Neuroimmunological
Diseases? Curr Med Chem 2007; 14(2318-2329.
Pedersen BK, Pedersen M, Krabbe KS, et al. Role of exercise-
induced brain-derived neurotrophic factor production
in the regulation of energy homeostasis in mammals. Exp
Physiol 2009;94(12): 1153-1160.
Bariohay B, Lebrun B, Moyse E, Jean A. Brain-Derived
Neurotrophic Factor Plays a Role as an Anorexigenic Factor
in the Dorsal Vagal Complex. Endocrinology 2005;146(12):
-5620.
Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic
factor functions as a metabotrophin to mediate the
effects of exercise on cognition. Eur J Neurosci 2008; 28(11):
-2287.
Aloe L, Tirassa P, Lambiase A. The topical application of
nerve growth factor as a pharmacological tool for human
corneal and skin ulcers. Pharmacol Res 57(4): 2008;253-
Karatzas A, Katsanos K, Lilis I, et al. NGF Promotes
Hemodynamic Recovery in a Rabbit Hindlimb Ischemic
Model Through trkA- and VEGFR2-dependent Pathways. J
Cardiovasc Pharmacol 2013;62(3): 270-277.
Meek TH, Wisse BE, Thaler JP, et al. BDNF action in the
brain attenuates diabetic hyperglycemia via insulin-independent
inhibition of hepatic glucose production. Diabetes
;62(5): 1512-1518.
Rao AA. Views and opinion on BDNF as a target for diabetic
cognitive dysfunction. Bioinformation 2013; 9(11): 551-554.
Lebrun B, Bariohay B, Moyse E, Jean A. Brain-derived
neurotrophic factor (BDNF) and food intake regulation: A
minireview. Auton Neurosci 2006;127:30-38.
Nicholson JR, Peter J-C, Lecourt A-C, et al. Melanocortin-4
Receptor Activation Stimulates Hypothalamic Brain-
Derived Neurotrophic Factor Release to Regulate Food
Intake, Body Temperature and Cardiovascular Function. J
Neuroendocrinol 2007;19(12): 974-982.
Fujinami A, Ohta K, Obayashi H, et al. Serum brain-derived
neurotrophic factor in patients with type 2 diabetes
mellitus: Relationship to glucose metabolism and biomarkers
of insulin resistance. Clin Biochem 41(10): 812-817,
Yamanaka M, Itakura Y, Tsuchida A, et al. Comparison of
the antidiabetic effects of brain-derived neurotrophic factor
and thiazolidinediones in obese diabetic mice. Diabet
Obes Metab 2007; 9(6): 879-888.
Chaldakov GN, Vankov VN. Morphological aspects of secretion
in the arterial smooth muscle cell, with special reference
to the golgi complex and microtubular cytoskeleton.
Atherosclerosis 1986;61(3): 175-192.
Chaldakov G. Human Body as a Multicrine System,
with Special Reference to Cell Protein Secretion: From
Vascular Smooth Muscles to Adipose Tissue. Biomed Rev
;27(VIII-XIX.
Yanev S, Fiore M, Hinev A, et al. From Antitubulins to
Trackins. Biomed Rev 2017;27:45-53.
Carito V, Venditti A, Bianco A, et al. Effects of olive leaf
polyphenols on male mouse brain NGF, BDNF and
their receptors TrkA, TrkB and p75. Natural Product Res
;28(22): 1970-1984.
Rotermund C, Machetanz G, Fitzgerald JC. The therapeutic
potential of metformin in neurodegenerative diseases.
Front Endocrinol 2018; 9: 400.
Cheng C, Lin CH, Tsai YW, Tsai CJ, Chou PH, Lan TH.
Type 2 diabetes and antidiabetic medications in relation to
dementia diagnosis. J Gerontol Ser A Biol Sci Med Sci 2014;
: 1299–1305.
Guo M, Mi J, Jiang QM, Xu JM, Tang YY, Tian G, et al.
Metformin may produce antidepressant effects through
improvement of cognitive function among depressed patients
with diabetes mellitus. Clin Exp Pharmacol Physiol
, 41, 650–656.
Ng TP, Feng L, Yap KB, Lee TS, Tan CH, Winblad B. Longterm
metformin usage and cognitive function among older
adults with diabetes. J Alzheimer’s Dis 2014, 41, 61–68.
El Massry M, Alaeddine LM, Ali L, Saad C, Eid AA.
Metformin: A growing journey from glycemic control to
the treatment of Alzheimer‘s disease and depression. Curr
Med Chem 2021;28(12):2328-2345. DOI: 10.2174/0929867
Cardoso S, Moreira PI. Antidiabetic drugs for Alzheimer‘s
and Parkinson‘s diseases: Repurposing insulin, metformin,
and thiazolidinediones. Int Rev Neurobiol 2020;155:37-64.
DOI: 10.1016/bs.irn.2020.02.010
Muñoz-Arenas G, Pulido G, Treviño S, Vázquez-Roque R,
Flores G, et al. Effects of metformin on recognition memory
and hippocampal neuroplasticity in rats with metabolic
syndrome. Synapse 2020;74(9):e22153. DOI: 10.1002/
syn.22153
Lester-Coll N, Rivera EJ, Soscia SJ, et al. Intracerebral streptozotocin
model of type 3 diabetes: Relevance to sporadic
Alzheimer’s disease. J Alzheimer’s Dis 2006;9:13-33.
Frisardi V, Solfrizzi V, Seripa D, Capurso C, Santamato A,
Sancarlo D, et al. Metabolic-Cognitive Syndrome: A Crosstalk
between Metabolic Syndrome and Alzheimer’s Disease.
Ageing Res Rev 2010;
Giordano V, Peluso G, Iannuccelli M, Benatti P, Nicolai R,
Calvani M. Systemic and brain metabolic dysfunction as a
new paradigm for approaching Alzheimer’s dementia. Neurochem
Res 2007;32:555-567.
Frohlich J, Chaldakov GN, Vinciguerra M. Cardio- and
neurometabolic adipobiology: Consequences and implications
for therapy. Int J Mol Sci 2021; 22(8): 4137.
DOI:10.3390/ijms22084137
Chaldakov GN, Aloe A, Rancic G, Pancheva RZ, Hiriart
M, Fiore M, Yanev S. Chapter 16. The Relevance of
Metabotrophic Factors in Pathobiology and Therapy of
Obesity and Related Diseases. In: P.S. Tappia et al. (eds.),
Cellular and Biochemical Mechanisms of Obesity, Advances
in Biochemistry in Health and Disease 23. Springer Nature
Switzerland AG 2021. DOI:10.1007/978-3-030-84763-0_16
Lee Y-H, Tharp WG, Maple RL, et al. Amyloid Precursor
Protein Expression Is Upregulated in Adipocytes in
Obesity. Obesity 2008;16(7): 1493-1500.
Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose
tissue-derived mesenchymal stem cells secrete functional
neprilysin-bound exosomes. Sci Rep 2013;3:1197.
Raine L, Drollette E, Kao S-C, Westfall D, Chaddock-
Heyman L, Kramer AF, et al. The associations between
adiposity, cognitive function, and achievement in children.
Med Sci Sports Exerc 2-18;. 50 (9): 1868–1874.
Lucci B. The contribution of Gaetano Perusini to the definition
of Alzheimer‘s disease. Ital J Neurol Sci 1998;19:49-52.
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