123 results on '"Mulè, Flavia"'
Search Results
102. 963 Influence by Glucagon-Like Peptide-2 (GLP-2) on Spontaneous Mechanical Activity and Electrically-Evoked Cholinergic Contractions in Mouse Proximal Colon
- Author
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Rotondo, Alessandra, Amato, Antonella, Serio, Rosa, and Mule', Flavia
- Published
- 2010
- Full Text
- View/download PDF
103. IMPACT OF HONEY REGULAR INTAKE ON NEURODEGENERATION IN AN ANIMAL MODEL WITH DIET-INDUCED OBESITY.
- Author
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TERZO, Simona, MULÈ, Flavia, CALVI, Pasquale, and AMATO, Antonella
- Subjects
- *
ANIMAL models in research , *NEURODEGENERATION , *OBESITY - Published
- 2021
104. Excitatory effects of opiates on the spontaneous EMG activity in pigeon oesophagus
- Author
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Mulè, Flavia, primary, Fileccia, Rosaria, additional, Postorino, Alessandra, additional, Serio, Rosa, additional, and Abbadessa-Urso, Salvatore, additional
- Published
- 1988
- Full Text
- View/download PDF
105. Functional evidence for different roles of GABAA and GABAB receptors in modulating mouse gastric tone
- Author
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Rotondo, Alessandra, Serio, Rosa, and Mulè, Flavia
- Subjects
- *
GABA receptors , *GASTRIC diseases , *AMINOBUTYRIC acid , *LABORATORY mice , *GASTRIC emptying , *ENZYMES , *NITRIC oxide - Abstract
Abstract: The aims of the present study were to investigate, using mouse whole stomach in vitro, the effects of γ-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABAA-receptor antagonist, bicuculline, potentiated by phaclofen, GABAB-receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABAC-receptor antagonist. Muscimol, GABAA-receptor agonist, mimicked GABA effects inducing relaxation, which was significantly reduced by bicuculline, Nω-nitro-l-arginine methyl ester (l-NAME), inhibitor of NO synthase or apamin, inhibitor of small conductance Ca2+-dependent K+ channels, which blocks the purinergic transmission in this preparation. It was abolished by tetrodotoxin (TTX) or l-NAME plus apamin. Baclofen, a specific GABAB-receptor agonist, induced an increase in the gastric tone, which was antagonized by phaclofen and abolished by TTX or atropine. Bicuculline, but not phaclofen or TPMPA, per se induced an increase in gastric tone, which was prevented by l-NAME. In conclusion, our results suggest that GABA is involved in the regulation of mouse gastric tone, through modulation of intrinsic neurons. Activation of GABAA-receptors mediates relaxation through neural release of NO and neurotransmitters, activating Ca2+-dependent K+ channels, likely purines, while activation of GABAB-receptors leads to contraction through acetylcholine release. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
106. Indicaxanthin from Opuntia ficus-indica Fruit Ameliorates Glucose Dysmetabolism and Counteracts Insulin Resistance in High-Fat-Diet-Fed Mice
- Author
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Simona Terzo, Alessandro Attanzio, Pasquale Calvi, Flavia Mulè, Luisa Tesoriere, Mario Allegra, Antonella Amato, Terzo S., Attanzio A., Calvi P., Mulè Flavia., Tesoriere L., Allegra M., and Amato A.
- Subjects
Opuntia ficus-indica ,obesity ,Physiology ,indicaxanthin ,phytochemicals ,insulin resistance ,inflammation ,oxidative stress ,dysmetabolism ,Clinical Biochemistry ,Cell Biology ,RM1-950 ,Biochemistry ,Dysmetabolism ,Oxidative stress ,Therapeutics. Pharmacology ,Molecular Biology - Abstract
Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between inflammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remarkable, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions.
- Published
- 2022
107. Nose-to-brain delivery of insulin enhanced by a nanogel carrier.
- Author
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Picone, Pasquale, Sabatino, Maria Antonietta, Ditta, Lorena Anna, Amato, Antonella, San Biagio, Pier Luigi, Mulè, Flavia, Giacomazza, Daniela, Dispenza, Clelia, and Di Carlo, Marta
- Subjects
- *
NANOGELS , *TREATMENT of neurodegeneration , *BLOOD-brain barrier , *INSULIN therapy , *DRUG delivery systems - Abstract
Recent evidences suggest that insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a suitable carrier and an appropriate route of administration are required to increase the efficacy and safety of the treatment. Here, poly( N -vinyl pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and with covalently attached insulin (NG-In) were characterized for biocompatibility and brain delivery features in a mouse model. Preliminarily, the biodistribution of the “empty” nanocarrier after intraperitoneal (i.p.) injection was investigated by using a fluorescent-labeled NG. By fluorescence spectroscopy, SEM and dynamic light scattering analyses we established that urine clearance occurs in 24 h. Histological liver and kidneys inspections indicated that no morphological alterations of tissues occurred and no immunological response was activated after NG injection. Furthermore, after administration of the insulin-conjugated nanogels (NG-In) through the intranasal route (i.n.) no alteration or immunogenic response of the nasal mucosa was observed, suggesting that the formulation is well tolerated in mouse. Moreover, an enhancement of NG-In delivery to the different brain areas and of its biological activity, measured as Akt activation levels, with reference to free insulin administration was demonstrated. Taken together, these results indicate that the synthesized NG-In enhances brain insulin delivery upon i.n. administration and strongly encourage its further evaluation as therapeutic agent against some neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
108. Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility
- Author
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Martina Martorana, Flavia Mulè, Antonella Amato, Pierenrico Marchesa, Angela Maffongelli, Simona Terzo, S. Scoglio, Amato A, Terzo S, Marchesa P, Maffongelli A, Martorana M, Scoglio S, and Mulè Flavia
- Subjects
Male ,Colon ,motility discomfort ,Methysergide ,Gene Expression ,Pharmacology ,Article ,PEA ,Contractility ,TAAR1 ,medicine ,Serotonin receptor antagonist ,Aphanizomenon ,Humans ,TX341-641 ,Myenteric plexus ,Aged ,human colon contractility ,Aged, 80 and over ,Biological Products ,AFA extract ,Nutrition and Dietetics ,Dose-Response Relationship, Drug ,Chemistry ,Nutrition. Foods and food supply ,Parasympatholytics ,EPPTB ,Muscle, Smooth ,Klamin® ,Middle Aged ,Immunohistochemistry ,Mechanism of action ,Dietary Supplements ,Enteric nervous system ,Female ,Peristalsis ,medicine.symptom ,Biomarkers ,β-PEA ,Food Science ,medicine.drug ,Muscle Contraction - Abstract
The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.
- Published
- 2021
109. Altered insulin pathway compromises mitochondrial function and quality control both in in vitro and in vivo model systems
- Author
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Flavia Mulè, Giacoma Galizzi, Luca Caruana, Alice Conigliaro, Riccardo Alessandro, Marta Di Carlo, Pasquale Massimo Picone, Laura Palumbo, Domenico Nuzzo, Simona Terzo, Antonella Amato, Galizzi G., Palumbo L., Amato A., Conigliaro A., Nuzzo D., Terzo S., Caruana L., Picone P., Alessandro R., Mulè Flavia., and Di Carlo M.
- Subjects
Male ,Aging ,Amyloid beta-Peptide ,medicine.medical_treatment ,Metabolic disease ,PINK1 ,Insulin pathway, Neurodegeneration, Metabolic diseases, Mitochondrion, Mitophagy, Aging ,Mitochondrion ,Diet, High-Fat ,Parkin ,NO ,Mice ,Insulin resistance ,Metabolic Diseases ,Cell Line, Tumor ,Mitophagy ,medicine ,Animals ,Humans ,Insulin ,Neurodegeneration ,Molecular Biology ,Amyloid beta-Peptides ,biology ,Animal ,Chemistry ,Cell Biology ,medicine.disease ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,Insulin receptor ,Mitochondrial permeability transition pore ,biology.protein ,Molecular Medicine ,Insulin Resistance ,Insulin pathway ,Human ,Signal Transduction - Abstract
Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and activation of mitophagy, proved by the rise of PINK1 and Parkin proteins. Nevertheless, in vitro, the increase of p62 and LC3 indicated an alteration in autophagy, while, in vivo decreased expression of p62 and increase of LC3 suggested removing of damaged mitochondria. Finally, in aged mice (28 and 48 weeks), the data indicated impairment of mitophagy and suggested the accumulation of damaged mitochondria. Taken together these outcomes indicate that alteration of the insulin pathway affects mitochondrial integrity, and effective mitophagy is age-dependent.
- Published
- 2021
110. From obesity to Alzheimer's disease through insulin resistance
- Author
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Flavia Mulè, Antonella Amato, Simona Terzo, Terzo S., Amato A., and Mulè Flavia.
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,medicine.disease_cause ,Endocrinology ,Insulin resistance ,Downregulation and upregulation ,Alzheimer Disease ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Dementia ,Obesity ,Neurodegeneration ,Inflammation ,business.industry ,Brain ,Alzheimer's disease ,medicine.disease ,Diabetes Mellitus, Type 2 ,Lipotoxicity ,business ,Oxidative stress - Abstract
Alzheimer's disease is one of the most frequent forms of dementia. It is a progressive neurodegenerative disease, characterized by presence of amyloid plaques and neurofibrillary tangles in the brain. Obesity is regarded as abnormal fat accumulation with deleterious impact on human health. There is full scientific evidence that obesity and the metabolic comorbidities (e.g., insulin resistance, hyperglycaemia, and type 2 diabetes) are related to Alzheimer's disease and likely in the causative pathway. Numerous studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation. In this review, we present how obesity and the associated lipotoxicity as well as chronic inflammation initiate a state of insulin resistance that in turn, may have a role in causing the characteristic cerebral alterations of AD. In particular, we focus on the molecular mechanisms linking the obesity-induced impairment in insulin signalling to the upregulation of Aβ aggregation, tau hyper-phosphorylation, inflammation, oxidative stress and mitochondrial dysfunction.
- Published
- 2021
111. A 1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels
- Author
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Zizzo, Maria Grazia, Bonomo, Alessandra, Belluardo, Natale, Mulè, Flavia, and Serio, Rosa
- Subjects
- *
PURINERGIC receptors , *ADENOSINES , *POTASSIUM channels , *ILEUM , *LABORATORY mice , *MUSCLE contraction , *ENTERIC nervous system - Abstract
Abstract: Aims: We investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects. Main methods: Mechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension. Key findings: Adenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone. Significance: Adenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
112. Protective potential of glucagon like peptide 2 (GLP-2) against the neurodegeneration
- Author
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Antonella Amato, Flavia Mulè, Amato, Antonella, and Mulè, Flavia
- Subjects
business.industry ,Neurodegeneration ,Pharmacology ,medicine.disease ,Glucagon-like peptide-2 ,Settore BIO/09 - Fisiologia ,lcsh:RC346-429 ,neuroinflammation ,Glucagon like peptide 2 (GLP-2) ,neurodegenerative disease ,Developmental Neuroscience ,Perspective ,medicine ,oxidative stress ,business ,lcsh:Neurology. Diseases of the nervous system - Abstract
Neurodegeneration consists in loss of neuron specific types, pattern and distribution, leading to progressive dysfunctions of the central nervous system. Neurodegenerative diseases include diverse pathological conditions, among which Alzheimer’s and Parkinson’s diseases are the most prevalent ones. Alzheimer’s disease is known as a growing dementia, characterized by progressive language, memory, and cognitive loss, while Parkinson’s disease is primarily characterized as a motor disorder. Senile plaques, caused by amyloid β peptide, hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of Alzheimer’s disease. Amyloid β oligomer formation is associated with development of reactive oxygen and nitrogen species, inflammation, calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions related with learning and memory. Parkinson’s disease is produced by dopaminergic neuron deterioration in the extrapyramidal tract of the midbrain. Accumulation of α-synuclein proteins (Lewy bodies) in the central, autonomic, and peripheral nervous system is the hallmark of the Parkinson’s disease. The Levy bodies break the neuronal membrane leading to neuronal death through oxidative stress, excitotoxicity, energy failure and neuroinflammation.
- Published
- 2019
113. Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains
- Author
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Martin R. Larsen, Giulia Accardi, Pia Jensen, Peter James, Antonella Amato, Flavia Mulè, Valentina Siino, Sonya Vasto, and Siino Valentina, James Peter, Vasto Sonya, Amato Antonella, Mulè Flavia, Accardi Giulia, Rossel Larsen Martin
- Subjects
0301 basic medicine ,medicine.medical_specialty ,RC620-627 ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Tau protein ,Obesity, nutrition, brain impairment, proteomics, post-translational modifications ,Brain damage ,Mitochondrion ,Proteomics ,medicine.disease_cause ,Settore BIO/09 - Fisiologia ,03 medical and health sciences ,proteomics ,0302 clinical medicine ,Internal medicine ,post-translational modifications ,medicine ,TX341-641 ,Obesity ,Nutritional diseases. Deficiency diseases ,Original Research ,Settore MED/04 - Patologia Generale ,Nutrition and Dietetics ,biology ,Nutrition. Foods and food supply ,Insulin ,Neurodegeneration ,medicine.disease ,brain impairment ,Insulin receptor ,nutrition ,030104 developmental biology ,Endocrinology ,biology.protein ,medicine.symptom ,030217 neurology & neurosurgery ,Oxidative stress ,Food Science - Abstract
Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment.
- Published
- 2021
114. Honey and obesity-related dysfunctions: a summary on health benefits
- Author
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Flavia Mulè, Simona Terzo, Antonella Amato, and Terzo Simona, Mulè Flavia, Amato Antonella.
- Subjects
0301 basic medicine ,Health Status ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Anti-Inflammatory Agents ,Adipose tissue ,Glycemic Control ,medicine.disease_cause ,Bioinformatics ,Biochemistry ,Antioxidants ,03 medical and health sciences ,0302 clinical medicine ,Hydroxybenzoates ,Animals ,Humans ,Medicine ,Obesity ,Neurodegeneration ,Molecular Biology ,Glycemic ,Flavonoids ,Inflammation ,Metabolic Syndrome ,Hyperplasia ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,fungi ,Metabolic disorder ,Polyphenols ,food and beverages ,Neurodegenerative Diseases ,Honey ,medicine.disease ,Oxidative Stress ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Hypertension ,Oxidative stre ,Insulin Resistance ,Metabolic syndrome ,business ,Lipid profile ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Honey is a natural product, containing flavonoids and phenolic acids, appreciated for its therapeutic abilities since ancient times. Although the bioactive potential is linked to the composition, that is variable depending on mainly the botanical origin, honey has antioxidant and anti-inflammatory properties. Therefore, honey, administered alone or in combination with conventional therapy, might result useful in the management of chronic diseases that are commonly associated with oxidative stress and inflammation state. Obesity is a metabolic disorder characterized by visceral adiposity. The adipose tissue becomes hypertrophic and undergoes hyperplasia, resulting in a hypoxic environment, oxidative stress and production of pro-inflammatory mediators that can be responsible for other disorders, such as metabolic syndrome and neurodegeneration. Experimental evidence from animals have shown that honey improves glycemic control and lipid profile with consequent protection from endothelial dysfunction and neurodegeneration. The purpose of the present review is to summarize the current literature concerning the beneficial effects of honey in the management of the obesity-related dysfunctions, including neurodegeneration. Based on the key constituents of honey, the paper also highlights polyphenols to be potentially responsible for the health benefits of honey. Further well-designed and controlled studies are necessary to validate these benefits in humans.
- Published
- 2020
115. Glucagon-like peptide-2 reduces the obesity-associated inflammation in the brain
- Author
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Sara Baldassano, Pasquale Picone, Marta Di Carlo, Flavia Mulè, Giacoma Galizzi, Domenico Nuzzo, Gaetano Felice Caldara, Antonella Amato, Nuzzo, Domenico, Baldassano, Sara, Amato, Antonella, Picone, Pasquale, Galizzi, Giacoma, Caldara, Gaetano Felice, Di Carlo, Marta, and Mulè, Flavia
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Inflammation ,medicine.disease_cause ,Diet, High-Fat ,Settore BIO/09 - Fisiologia ,Neuroprotection ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,Neuroinflammation ,Internal medicine ,medicine ,Glucagon-Like Peptide 2 ,Animals ,Obesity ,Neurodegeneration ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,TUNEL assay ,Glial fibrillary acidic protein ,biology ,Chemistry ,digestive, oral, and skin physiology ,Brain ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Neuroprotective Agents ,Neurology ,Gliosis ,Oxidative stress ,Astrocytes ,biology.protein ,Glucagon-Like Peptide-2 Receptor ,Oxidative stre ,Encephalitis ,medicine.symptom ,Inflammation Mediators ,GLP-2 ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists - Abstract
Growing evidence suggests a link between obesity and neurodegeneration. The purpose of the present study was to explore the neuroprotective potential of glucagon-like peptide-2 (GLP-2) in the brain of high fat diet (HFD)-fed mice. Markers of inflammation and oxidative stress were analysed in the brains of obese mice chronically treated with [Gly2]-GLP-2 (teduglutide), the stable analogue of the GLP-2, and they were compared to age-matched untreated obese and lean animals. Neurodegeneration was examined by TUNEL assay. HFD feeding increased the expression of pro-inflammatory mediators (NF-kB, IL-8, TNF-α, IL-1β and IL-6), glial fibrillary acidic protein (GFAP), index of gliosis and neurodegeneration, stress marker proteins (p-ERK, Hsp60 and i-NOS), amyloid-β precursor protein (APP). [Gly2]-GLP-2 treatment significantly attenuated the HFD-induced increased expression of the various markers, as well as the higher levels of reactive oxygen species found in brains of untreated-HFD mice. Immunofluorescence confirmed that the increase of GFAP or APP in the brain cortex of HFD mice were less prominent in the [Gly2]-GLP-2 treated group. TUNEL-positive cell number in brain sections of [Gly2]-GLP-2-treated HFD-fed mice was significantly lesser in comparison with untreated-HFD animals and similar to STD fed mice. In conclusion, the results of the present study suggest that GLP-2 stable analogue improves the obesity-associated neuroinflammation and the central stress conditions, it reduces the neuronal apoptotic death, providing evidence for a neuroprotective role of the peptide.
- Published
- 2018
116. Positive Impacts of Aphanizomenon Flos Aquae Extract on Obesity-Related Dysmetabolism in Mice with Diet-Induced Obesity.
- Author
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Terzo S, Calvi P, Giardina M, Gallizzi G, Di Carlo M, Nuzzo D, Picone P, Puleio R, Mulè F, Scoglio S, and Amato A
- Subjects
- Animals, Mice, Mice, Obese, Plant Extracts pharmacology, Plant Extracts therapeutic use, Obesity drug therapy, Obesity metabolism, Diet, High-Fat adverse effects, Inflammation drug therapy, Glucose, RNA, Messenger metabolism, Aphanizomenon metabolism
- Abstract
The present study evaluated the ability of KlamExtra
® , an Aphanizomenon flos aquae (AFA) extract, to counteract metabolic dysfunctions due to a high fat diet (HFD) or to accelerate their reversion induced by switching an HFD to a normocaloric diet in mice with diet-induced obesity. A group of HFD mice was fed with an HFD supplemented with AFA (HFD-AFA) and another one was fed with regular chow (standard diet-STD) alone or supplemented with AFA (STD-AFA). AFA was able to significantly reduce body weight, hypertriglyceridemia, liver fat accumulation and adipocyte size in HFD mice. AFA also reduced hyperglycaemia, insulinaemia, HOMA-IR and ameliorated the glucose tolerance and the insulin response of obese mice. Furthermore, in obese mice AFA normalised the gene and the protein expression of factors involved in lipid metabolism (FAS, PPAR-γ, SREBP-1c and FAT-P mRNA), inflammation (TNF-α and IL-6 mRNA, NFkB and IL-10 proteins) and oxidative stress (ROS levels and SOD activity). Interestingly, AFA accelerated the STD-induced reversion of glucose dysmetabolism, hepatic and VAT inflammation and oxidative stress. In conclusion, AFA supplementation prevents HFD-induced dysmetabolism and accelerates the STD-dependent recovery of glucose dysmetabolism by positively modulating oxidative stress, inflammation and the expression of the genes linked to lipid metabolism.- Published
- 2023
- Full Text
- View/download PDF
117. From obesity to Alzheimer's disease through insulin resistance.
- Author
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Terzo S, Amato A, and Mulè F
- Subjects
- Brain, Humans, Inflammation complications, Alzheimer Disease complications, Diabetes Mellitus, Type 2 complications, Insulin Resistance, Obesity complications
- Abstract
Alzheimer's disease is one of the most frequent forms of dementia. It is a progressive neurodegenerative disease, characterized by presence of amyloid plaques and neurofibrillary tangles in the brain. Obesity is regarded as abnormal fat accumulation with deleterious impact on human health. There is full scientific evidence that obesity and the metabolic comorbidities (e.g., insulin resistance, hyperglycaemia, and type 2 diabetes) are related to Alzheimer's disease and likely in the causative pathway. Numerous studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation. In this review, we present how obesity and the associated lipotoxicity as well as chronic inflammation initiate a state of insulin resistance that in turn, may have a role in causing the characteristic cerebral alterations of AD. In particular, we focus on the molecular mechanisms linking the obesity-induced impairment in insulin signalling to the upregulation of Aβ aggregation, tau hyper-phosphorylation, inflammation, oxidative stress and mitochondrial dysfunction., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
118. Altered insulin pathway compromises mitochondrial function and quality control both in in vitro and in vivo model systems.
- Author
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Galizzi G, Palumbo L, Amato A, Conigliaro A, Nuzzo D, Terzo S, Caruana L, Picone P, Alessandro R, Mulè F, and Di Carlo M
- Subjects
- Amyloid beta-Peptides genetics, Amyloid beta-Peptides metabolism, Animals, Cell Line, Tumor, Diet, High-Fat adverse effects, Humans, Insulin Resistance, Male, Mice, Mice, Inbred C57BL, Signal Transduction, Insulin metabolism, Mitochondria metabolism
- Abstract
Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and activation of mitophagy, proved by the rise of PINK1 and Parkin proteins. Nevertheless, in vitro, the increase of p62 and LC3 indicated an alteration in autophagy, while, in vivo decreased expression of p62 and increase of LC3 suggested removing of damaged mitochondria. Finally, in aged mice (28 and 48 weeks), the data indicated impairment of mitophagy and suggested the accumulation of damaged mitochondria. Taken together these outcomes indicate that alteration of the insulin pathway affects mitochondrial integrity, and effective mitophagy is age-dependent., (Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
119. Glucagon-like peptide-2 analog and inflammatory state in obese mice.
- Author
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Baldassano S, Amato A, Terzo S, Caldara GF, Lentini L, and Mulè F
- Subjects
- Animals, Glucagon-Like Peptide-1 Receptor, Insulin, Mice, Mice, Obese, Peptide Fragments, Glucagon-Like Peptide 1, Glucagon-Like Peptide 2
- Published
- 2020
- Full Text
- View/download PDF
120. Protective potential of glucagon like peptide 2 (GLP-2) against the neurodegeneration.
- Author
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Amato A and Mulè F
- Abstract
Competing Interests: None
- Published
- 2019
- Full Text
- View/download PDF
121. Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro.
- Author
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Baldassano S, Wang GD, Mulè F, and Wood JD
- Subjects
- Acetylcholine metabolism, Animals, Carbachol pharmacology, Choline O-Acetyltransferase metabolism, Cytoplasm metabolism, ELAV Proteins metabolism, Electric Conductivity, Electric Stimulation, Electrophysiological Phenomena drug effects, Electrophysiological Phenomena physiology, Glucagon-Like Peptide 1 antagonists & inhibitors, Glucagon-Like Peptide-1 Receptor, Guinea Pigs, Hexamethonium pharmacology, Ileum drug effects, Ileum innervation, Ileum metabolism, In Vitro Techniques, Intestinal Mucosa drug effects, Intestine, Small drug effects, Intestine, Small innervation, Male, Neurons drug effects, Neurons metabolism, Neuropeptide Y metabolism, Peptide Fragments pharmacology, Receptors, Glucagon metabolism, Receptors, Vasoactive Intestinal Polypeptide, Type I antagonists & inhibitors, Scopolamine pharmacology, Somatostatin metabolism, Vasoactive Intestinal Peptide metabolism, Vasoactive Intestinal Peptide pharmacology, Chlorides metabolism, Glucagon-Like Peptide 1 pharmacology, Intestinal Mucosa innervation, Intestinal Mucosa metabolism, Intestine, Small metabolism
- Abstract
Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat-sheet preparations in Ussing chambers did not change baseline short-circuit current (I(sc)), which served as a marker for chloride secretion. Transmural EFS evoked neurally mediated biphasic increases in I(sc) that had an initial spike-like rising phase followed by a sustained plateau-like phase. Blockade of the EFS-evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-1 receptor antagonist exendin-(9-39) suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic or vasoactive intestinal peptide receptor antagonists but not in the presence of a muscarinic receptor antagonist. GLP-1 significantly reduced EFS-evoked ACh release. In the submucosal plexus, GLP-1R immunoreactivity (IR) was expressed by choline acetyltransferase-IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons, and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and that its activation leads to a decrease in neurally evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions in the enteric neural networks that control secretomotor functions.
- Published
- 2012
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122. Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro.
- Author
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Baldassano S, Liu S, Qu MH, Mulè F, and Wood JD
- Subjects
- Acetylcholine metabolism, Animals, Choline O-Acetyltransferase metabolism, Electric Stimulation, Enteric Nervous System drug effects, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Glucagon-Like Peptide-2 Receptor, Guinea Pigs, Ileum drug effects, Ileum metabolism, Immunohistochemistry, In Vitro Techniques, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, Male, Membrane Potentials, Neuropeptide Y metabolism, Neurotransmitter Agents pharmacology, Receptors, Glucagon antagonists & inhibitors, Receptors, Glucagon metabolism, Somatostatin metabolism, Time Factors, Vasoactive Intestinal Peptide metabolism, Chlorides metabolism, Enteric Nervous System metabolism, Glucagon-Like Peptide 2 metabolism, Ileum innervation, Intestinal Mucosa innervation, Intestinal Secretions metabolism
- Abstract
Glucagon-like peptide-2 (GLP-2) is an important neuroendocrine peptide in intestinal physiology. It influences digestion, absorption, epithelial growth, motility, and blood flow. We studied involvement of GLP-2 in intestinal mucosal secretory behavior. Submucosal-mucosal preparations from guinea pig ileum were mounted in Ussing chambers for measurement of short-circuit current (I(sc)) as a surrogate for chloride secretion. GLP-2 action on neuronal release of acetylcholine was determined with ELISA. Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was studied with immunohistochemical methods. Application of GLP-2 (0.1-100 nM) to the serosal or mucosal side of the preparations evoked no change in baseline I(sc) and did not alter transepithelial ionic conductance. Transmural electrical field stimulation (EFS) evoked characteristic biphasic increases in I(sc), with an initially rapid rising phase followed by a sustained phase. Application of GLP-2 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-2R antagonist GLP-2-(3-33) significantly reversed suppression of the EFS-evoked responses by GLP-2. Tetrodotoxin, scopolamine, and hexamethonium, but not vasoactive intestinal peptide type 1 receptor (VPAC1) antagonist abolished or reduced to near zero the EFS-evoked responses. GLP-2 suppressed EFS-evoked acetylcholine release as measured by ELISA. Pretreatment with GLP-2-(3-33) offset this action of GLP-2. In the submucosal plexus, GLP-2R immunoreactivity (-IR) was expressed in choline acetyltransferase-IR neurons, somatostatin-IR neurons, neuropeptide Y-IR neurons, and vasoactive intestinal peptide-IR neurons. We conclude that submucosal neurons in the guinea pig ileum express GLP-2R. Activation of GLP-2R decreases neuronally evoked epithelial chloride secretion by suppressing acetylcholine release from secretomotor neurons.
- Published
- 2009
- Full Text
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123. Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice).
- Author
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Vannucchi MG, Zizzo MG, Zardo C, Pieri L, Serio R, Mulè F, and Faussone-Pellegrini MS
- Subjects
- Animals, Disease Models, Animal, Electrophysiology, Immunohistochemistry, Male, Mice, Mice, Inbred mdx, Microscopy, Electron, Muscle, Smooth pathology, Muscle, Smooth ultrastructure, Myenteric Plexus physiology, Myenteric Plexus ultrastructure, Proto-Oncogene Proteins c-kit metabolism, Stomach physiology, Dystrophin deficiency, Muscle, Smooth physiology, Muscular Dystrophies physiopathology, Stomach cytology, Stomach pathology
- Abstract
At least two populations of c-kit positive interstitial cells of Cajal (ICC) lie in the gastric wall, one located at the myenteric plexus level has a pace-making function and the other located intramuscularly is intermediary in the neurotransmission and regenerates the slow waves. Both of these ICC sub-types express full-length dystrophin. Mdx mice, an animal model lacking in full-length dystrophin and used to study Duchenne muscular dystrophy (DMD), show gastric dismotilities. The aim of the present study was to verify in mdx mice whether: (i) gastric ICC undergo morphological changes, through immunohistochemical and ultrastructural analyses; and (ii) there are alterations in the electrical activity, using intracellular recording technique. In control mice, ICC sub-types showed heterogeneous ultrastructural features, either intramuscularly or at the myenteric plexus level. In mdx mice, all of the ICC sub-types underwent important changes: coated vesicles were significantly more numerous and caveolae significantly fewer than in control; moreover, cytoskeleton and smooth endoplasmic reticulum were reduced and mitochondria enlarged. c-Kit-positivity and integrity of the ICC networks were maintained. In the circular muscle of normal mice slow waves, which consisted of initial and secondary components, occurred with a regular frequency. In mdx mice, slow waves occurred in a highly dysrhythmic fashion and they lacked a secondary component. We conclude that the lack of the full-length dystrophin is associated with ultrastructural modifications of gastric ICC, most of which can be interpreted as signs of new membrane formation and altered Ca(2+) handling, and with defective generation and regeneration of slow wave activity.
- Published
- 2004
- Full Text
- View/download PDF
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