Dottorato in Fisiopatologia Medica

Contatti

Supervisore

Ezio Ghigo
Riccarda Granata

Tesi di dottorato

Title: Effects of the ghrelin gene-derived peptides on  browning and thermogenesis

Abstract:

White adipose tissue (WAT) is the main energy reservoir of the body, while brown adipose tissue (BAT) dissipates energy through heat production, a process mainly regulated by mitochondrial uncoupling protein-1 (UCP-1). BAT plays a pivotal role in thermogenesis, acting as a defence against cold and positive regulator of metabolic functions. Therefore, strategies aimed at promoting BAT activation and WAT browning may constitute a therapeutic option for the treatment of obesity and metabolic dysfunctions. The ghrelin gene-derived peptides, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Obe), are key regulators of energy homeostasis, as well as glucose and lipid metabolism. In vivo studies indicated that AG, via the growth hormone secretagogue receptor type 1a (GHS-R1a), in addition to promoting adipogenesis, inhibits UCP-1 mRNA expression in BAT and thermogenic functions. Conversely, UAG through a yet unknown receptor, and Obe, via the glucagon-like peptide 1 receptor (GLP-1R), exert positive metabolic functions. To date, however, the role of the ghrelin peptides in adipose browning and BAT functions is still unknown. Thus, we studied the effect of AG, UAG and Obe in the browning of mouse 3T3-L1 and human adipocytes. 3T3-L1 preadipocytes were differentiated into white adipocytes for 10 days (in whitening medium), then transdifferentiated for 72 h into beige cells (in browning medium), in either absence or presence of AG, UAG and Obe (500 nM each). Human mature adipocytes, isolated from subcutaneous (SAT) and visceral adipose tissue (VAT), were stimulated for 24 h with or without each peptide (500 nM). In 3T3-L1 cells, UAG and Obe, but not AG, increased the mRNA and protein levels of the BAT markers

 

Attività di ricerca

PhD Classes & Courses Attended

1st Year (2022)

Approaches to Scientific Research:

• 28 June 2022 - Precision Medicine in Oncology: Putting Drivers and Targets in Context – Prof. Livio Trusolino
• 30 June 2022 - How to Write a Scientific Paper – Prof. Riccarda Granata
• 07 July 2022 - Setting Up an In Vivo Experimental Model – Prof. Stefania Bruno
• 12 July 2022 - Fitting Regression Models: Interpretation of Regression Coefficients, Uncertainty Measures, and Hypothesis Testing – Prof. Milena Maule
• 19 July 2022 - Regression Models: From Linear to Generalized Linear Models. Interpretation of Interactions Between Predictors – Prof. Milena Maule
• 27 Sept 2022 - Scientific Presentations – Prof. Benedetta Bussolati

Pathophysiological Basis of Diseases:

• 21 June 2022 - Etiopathogenesis of Diabetic Retinopathy – Prof. Massimo Porta
• 05 July 2022 - Update on Physiology of Hypertension – Prof. Franco Veglio
• 06 Sept 2022 - Physiopathology of Diabetic Nephropathy – Prof. Gabriella Gruden
• 08 Sept 2022 - Targets for Functional Imaging in Medicine – Prof. Désirée Deandreis
• 15 Sept 2022 - Physiopathology of Autoimmune Hepatitis – Prof. Marilena Durazzo

2nd Year (2023)

Pathophysiological Basis of Diseases: Cardiovascular, Metabolism, and Oncology:

• 13 June 2023 - Cancer Survivors: Pathophysiology of Late-Effects and Challenges in Management – Prof. Emanuela Arvat
• 29 June 2023 - Diabetic Nephropathy – Prof. Gabriella Gruden
• 05 Sept 2023 - Extracellular Vesicles and Liquid Biopsy – Prof. Benedetta Bussolati
• 07 Sept 2023 - Impact of the Metabolic Syndrome on the Digestive Tract – Prof. Elisabetta Bugianesi

3rd Year (2024)

Pathophysiology and Innovative Therapeutic Approaches of Diseases:

• 21 May 2024 - Cancer Survivors: Pathophysiology of Late-Effects and Implications for Translational Applications – Prof. Emanuela Arvat
• 24 May 2024 - Pathophysiology of Cardiovascular Hemodynamics and Translational Application – Prof. Alberto Milan
• 27-29 May 2024 - Summarising Evidence from Multiple Studies – Prof. Aurelio Tobias, Visiting Professor, Spanish Council for Scientific Research (Host: Prof. Milena Maule, Department of Medical Science, University of Torino)
• 28 June 2024 - Therapeutic Strategies for Liver Transplant – Prof. Renato Romagnoli
• 03 July 2024 - Genetic Forms of Hypertension – Prof. Paolo Mulatero
• 10 Sept 2024 - Current and Future Directions of Kidney Transplantation – Prof. Luigi Biancone
• 18 Sept 2024 - Extracellular Vesicles and Regenerative Medicine – Prof. Alessia Brossa

E-Learning Courses

• Workshop on Advanced Cell and Gene Therapies, MBC, Turin
• General Training Course on Health and Safety for Workers
• Nature Masterclasses:
• Advancing Your Scientific Presentations
• Data Analysis: Conducting and Troubleshooting
• Writing and Publishing a Review Paper
• Writing a Research Paper
• Scientific Writing and Publishing
• Publishing a Research Paper

Conferences and Seminars Attended

• 25 Sept 2024 - Tools and Indicators in the Procedures for Evaluating and Analysing Scientific Output, University of Turin
• 27-29 May 2024 - Summarising Evidence from Multiple Studies, University of Turin, Turin, Italy
• 23 April 2024 - BioRender Workshop: Better Figures for Presentations, University of Turin, Turin, Italy
• 09 April 2024 - Innovation Office Impact Series 2024: Tools to Develop Innovative Ideas, University of Turin, Turin, Italy
• 22 Jan 2024 - Cryopreservation Best Practices for Cell & Gene Therapy Source Material, CCS, Turin, Italy
• 18 Dec 2023 - Breast Cancer Multiomic: Insights into Tumor Heterogeneity, BioSkytbs Genomics, Turin, Italy
• 28 June – 1 July 2023 - 42nd SIE National Congress, Rome, Italy
• 14-15 April 2023 - International Conference on Recent Advances in Health Sciences (ICRAHS-2023), Lovely Professional University, Punjab, India
• 21-24 May 2022 - 24th European Congress of Endocrinology (ECE), Milan, Italy
• 07-08 April 2022 - First International Workshop on Advanced Cell and Gene Therapies, MBC, Turin, Italy

Research Publications

1. Granato, G., Gesmundo, I., Pedrolli, F., Kasarla, R., Begani, L., Banfi, D., Bruno, S., Lopatina, T., Brizzi, M. F., Cai, R., Sha, W., Ghigo, E., Schally, A. V., & Granata, R. (2023). Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells. Frontiers in immunology, 14, 1231363. https://doi.org/10.3389/fimmu.2023.1231363.
2. Gesmundo, I., Pedrolli, F., Vitale, N., Bertoldo, A., Orlando, G., Banfi, D., Granato, G., Kasarla, R., Balzola, F., Deaglio, S., Cai, R., Sha, W., Papotti, M., Ghigo, E., Schally, A. V., & Granata, R. (2022). Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma. International journal of molecular sciences, 23(19),11248. https://doi.org/10.3390/ijms231911248

3. Kasarla R., Gesmundo, I., Congiusta, N., Sabbia, G., Pardini, B., Bocchiotti, M. A., Ghigo, E., & Granata, R. (2022). Glucocorticoids enhance browning and thermogenic functions of mouse and human white adipocytes. Endocrine Abstracts. DOI: 1530/endoabs.81.P604

1. Kashid, S., Suttee, A., Kadam, P., Khatik, G.L., Kasarla, R., (2022). An In- Silico Studies for Immunomodulatory Potential of Phytoconstituents from a Naturally Occurring Herb Nigella Sativa. Pharmacophore 13, 14–26. DOI: 10.51847/E6cKqdRhE4

5. Pulipaka, S., Suttee, A., Kumar, M. R., & Kasarla, R. (2023). Exploration of in-vitro antidiabetic activity of zno NPS and AG NPS synthesized using methanolic extracts of Alpinia Mutica and tradescantia spathaeca leaves. International journal of pharmaceutical quality assurance, 14(03), 464–469.https://doi.org/10.25258/ijpqa.14.3.01
6. Kashid, S., Suttee, A., Kadam, P., & Kasarla, R. (2023). In-silico assessment of potent immunomodulators from pimpinella anisum and its antioxidant potential. International journal of drug delivery technology, 13(03), 864–868. https://doi.org/10.25258/ijddt.13.3.15
7. Pulipaka, S., Suttee, A., Ravi Kumar, M., Shanker, K., Kasarla, R., Kasarla, S. (2024). Development of an Innovative Ultrasound-Assisted Extraction Technique to Optimize Extraction on Phytoconstituents and Compared Conventional Extraction Method. In: Pawar, P.M., et al.Techno-societal 2022, 127–134. ICATSA 2022. Springer, Cham. https://doi.org/10.1007/978-3-031-34644-6_14
8. Prashant,S,V., Abhishek, K., Pavani, P., Kasarla R, Suttee, A. (2023). Potential role of graphene oxide in diagnosis and treatment of breast cancer- an overview European Chemical Bulletin12(Special issue 4):10887-10900 DOI: 48047/ecb/2023.12.si4.984
9. Pulipaka, S. P., Suttee, A., Ravi Kumar, M., Kalakotla, S., Lobo, R., & Kasarla, R. (2022). In vitro pharmacognostical, phytochemical and pharmacological evaluation of Tradescantia spathacea: An Journal of Pharmaceutical Negative Results, 13(S01). https://doi.org/10.47750/pnr.2022.13.s01.110
10. Mahajan, P., Kashid, S., Pulipaka, S., Sharma, V., Kasarla, R., & Suttee, A. (2023, May). Possible insilico exploration of Alpinia mutica and Tradescantia spatheca for diabetes mellitus. European Chemical Bulletin.

 

 

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