Scholarship 24/17423-6 - Tecido adiposo, Obesidade - BV FAPESP
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Early obesity and hepatocellular carcinoma: unveiling the adipose tissue and liver carcinogenesis interplay

Grant number: 24/17423-6
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date until: January 03, 2025
End date until: January 02, 2026
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Luís Fernando Barbisan
Grantee:Gabriel Bacil Prata
Supervisor: Tim Greten
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Institution abroad: Center For Cancer Research, United States  
Associated to the scholarship:22/13402-9 - Effects of carboxymethylcellulose and polysorbate 80 food additive on hepatocarcinogenesis-associated non-alcoholic fatty liver disease., BP.DR

Abstract

Hepatocellular carcinoma (HCC) has become a major public health issue worldwide, corresponding to the 3rd deadliest and 6th most incident type of cancer. In the past few decades, the growing incidence of non-communicable diseases (e.g.: obesity and type 2 diabetes) was followed by an overwhelming epidemiological relevance of non-viral aetiologies-derived HCC, especially metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disease globally. Childhood overweight and obesity are progressively prevalent in early life and easily recurrent comorbidities targeted as risk factors for MASLD and HCC. During obesity onset, adipose tissue (AT)-derived mediators are targeted as persistent metabolic reprogrammers of myeloid-derived cells. These might exert pivotal effects on the hepatic tumoral immune microenvironment (TIM) and contribute to tumoral emergence. However, it is still elusive whether obesity might induce persistent effects on myeloid-derived cells and hepatocarcinogenesis over time. Thus, we intend to assess the persistent effects of early obesity on liver carcinogenesis, by unveiling the effects of AT macrophages (ATM) on the hepatic TIM. Mice will be fed a Western diet (WD) or a regular diet (RD) for 15 weeks. By the 6th week of protocol, WD-fed mice will be shifted to an RD protocol (shifted WD), being allocated into 3 groups (RD, WD, and SWD). At the 13th week of protocol, mice will be submitted to intrahepatic injections of RIL-175 (1x105 cells) for tumor emergence. By the 18th week, mice will be euthanized, and samples (hepatic, AT, and serum) will be collected for a histopathological assessment and further ATMs identification by a spectral flow cytometry strategy. Considering the ongoing hepatic scRNA/ATAC-seq findings of the host group, an integrative analysis of ATM and hepatic TIM interplay will be done.

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