Lipid Metabolism in Obesity, Diabetes and Cancer

Department of Biochemistry and Physiology

Faculty of Pharmacy and Food Sciences, UB

Laura Herrero
ORCID ID: 0000-0003-4244-4673
Tel +34 934024522

www.ub.edu/betaoxi

Principal investigators: Laura Herrero
María Zambrano postdoctoral fellow: Marijana Todorčević
CIBEROBN postdoctoral fellow: Mar Romero
MSCA postdoctoral fellow: Agustina Creus
Phd student: Ana Corral Marc Reina Ivonne Palacios Research assistant: Susana Redondo

Current
Research

Our group is interested in the molecular mechanisms implicated in the pathogenesis of obesity, type 2 diabetes and cancer. In particular, we study the role of fatty acids in metabolism, focusing on Carnitine Palmitoyltransferase I (CPTI), the key regulatory enzyme in mitochondrial fatty-acid oxidation. CPTI catalyses the rate-limiting step in the entry of cytosolic long-chain acyl-CoA into mitochondria, where β-oxidation takes place. Our research lines include the study of fatty-acid metabolism in:

1-Obesity-induced insulin resistance and type 2 diabetes (liver and white and brown adipose tissue).

2-Appetite (hypothalamus).

3-Development of potential new treatments for obesity, type 2 diabetes and cancer, through structural studies of CPTI-related drugs.

Technology to offer

1) Mice and rats
Stereotaxis and icv cannulation
Fat transplantation
ICV injection of viral vectors
FACS from blood and lymphocytes (liver, spleen and adipose tissue)
GTT and Pyruvate Tolerance Test (PTT)
Tissue insulin signaling
Tissue histology and IHC
Mitochondrial bioenergetics (Seahorse) in adipose tissue explants
Tissue and body thermogenesis (thermographic camera)
CPT1A flox mice

2) Virus

Tail vein injection of viral vectors (adenovirus and AAV)
Adenovirus and AAV of GFP, CPT1A and CPT1AM

4) Cellular cultures

Isolation of primary hepatocytes (mice & rats)
Isolation of adipose-derived MSCs (mice)
Isolation of primary cortical neurons (mice)
Fatty acid and glucose oxidation
Mitochondrial bioenergetics (Seahorse) in cell lines
Culture cells thermogenesis (thermographic camera)

5) Metabolite determinations

Acyl-CoA, malonyl-CoA and acyl-carnitine in tissues and cells (HPLC-MS/MS)
Ceramides, triglycerides, DAG
Tissue & cellular ROS and ATP
Serum cytokines, ketone bodies, FFA, insulin, leptin and ghrelin
Enzyme activity of CPT1

Selected
Publications

Orellana-Gavaldà, J. M.; Herrero, L.; Malandrino, M. I.; Pañeda, A.; Sol Rodríguez-Peña, M.; Petry, H.; Asins, G.; Van Deventer, S.; Hegardt, F. G.; Serra, D. Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation. Hepatology. 53(3), 821-832, 2011. doi.org/10.1002/hep.24140

Makowski, K.; Mir, J. F.; Mera, P.; Ariza, X.; Asins, G.; Hegardt, F. G.; Herrero, L.; García, J.; Serra, D. (-)-UB006: a new fatty acid synthase inhibitor and cytotoxic agent without anorexic side effects. European Journal of Medicinal Chemistry. 131:207-221, 2017. doi.org/10.1016/j.ejmech.2017.03.012

Calderon-Dominguez, M.; Alcalá, M.; Sebastián, D.; Zorzano, A.; Viana, M.; Serra, D.; Herrero, L. Brown adipose tissue bioenergetics: a new methodological approach. Advanced Science. 4(4):1600274, 2017. doi.org/10.1002/advs.201600274

Du, W.; Zhang, L.; Brett-Morris, A.; Aguila, B.; Kerner, J.; Hoppel, C. L.; Puchowicz, M.; Serra, D.; Herrero, L.; Rini, B.; Campbell, S.; Welford, S. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nature Communications. 8(1):1769, 2017. doi.org/10.1038/s41467-017-01965-8

Mir, J. F.; Zagmutt, S.; Lichtenstein, M. P.; García-Villoria, J.; Weber, M.; Gracia, A.; Fabriàs, G.; Casas, J.; López, M.; Casals, N.; Ribes, A.; Suñol, C.; Herrero, L.; Serra, D. Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex. Molecular Neurobiology. 55(9):7216-7228, 2018. doi.org/10.1007/s12035-018-0921-3

Selected
Publications

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Author

Identification

Orellana-Gavaldà JM, Herrero L, Malandrino MI, Pañeda A, Sol Rodríguez-Peña M, Petry H, Asins G, Van Deventer S, Hegardt FG, Serra D. Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation. Hepatology. 2011. doi: 10.1002/hep.24140.

[/su_spoiler] [su_spoiler title="" open="no" style="default" icon="plus" anchor="" class="selected-publications-toggle"]

Author

Identification

Makowski K, Mir JF, Mera P, Ariza X, Asins G, Hegardt FG, Herrero L, García J*, Serra D* (*Corresponding authors). (-)-UB006: a new fatty acid synthase inhibitor and cytotoxic agent without anorexic side effects. Eur J Med Chem. 2017.131:207-221. doi: 10.1016/j.ejmech.2017.03.012.

[/su_spoiler] [su_spoiler title="" open="no" style="default" icon="plus" anchor="" class="selected-publications-toggle"]

Author

Identification

Calderon-Dominguez M, Alcalá M, Sebastián D, Zorzano A, Viana M, Serra D, Herrero L. Brown adipose tissue bioenergetics: a new methodological approach. Advanced Science. 2017. 4(4):1600274. doi: 10.1002/advs.201600274.

 

[/su_spoiler] [su_spoiler title="" open="no" style="default" icon="plus" anchor="" class="selected-publications-toggle"]

Author

Identification

Du W, Zhang L, Brett-Morris A, Aguila B, Kerner J, Hoppel CL, Puchowicz M, Serra D, Herrero L, Rini B, Campbell S, Welford S. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nature Communications. 2017. 8(1):1769. doi: 10.1038/s41467-017-01965-8.

[/su_spoiler] [su_spoiler title="" open="no" style="default" icon="plus" anchor="" class="selected-publications-toggle"]

Author

Identification

Mir JF, Zagmutt S, Lichtenstein MP, García-Villoria J, Weber M, Gracia A, Fabriàs G, Casas J, López M, Casals N, Ribes A, Suñol C, Herrero L, Serra D. Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex. Mol Neurobiol. 2018. 55(9):7216-7228. doi: 10.1007/s12035-018-0921-3.

[/su_spoiler]