Implications of yacon (Smallanthus sonchifolius) root syrup on metabolic-associated Fatty Liver Disease

• Grant number: 22/16917-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2023
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luís Fernando Barbisan
• Grantee: Isadora Penedo de Souza
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects ~25% of the world's population, and it is closely associated with metabolic disorders, justifying NAFLD renomenclature to MAFLD (metabolic associated fatty liver disease). Furthermore, this complex condition - which has no approved medical treatment other than dietary re-education - is caused by western diet (WD), involving alterations not only in the hepatic axis, but also in adipose tissue (AT) and in the intestinal microbiome. In turn, yacon roots (Smallanthus sonchifolius), which are rich in fructans (60-70%) such as inulin and fructooligosaccharides (FOS), have already demonstrated antiobesogenic effects and prebiotic properties, despite not being yet evaluated in the context of MAFLD. Thus, we will evaluate whether the administration of yacon syrup attenuates MAFLD by modulating (1) hepatic, (2) intestinal and (3) adipose axis. We will also evaluate the effects of yacon treatment on dietary interventions reduced in lipids and sugar. Briefly, female C57BL/6 mice will be submitted to WD for 3 months (chow with 30% lard, 0.2% cholesterol and 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of d-fructose and d-glucose, respectively). After this period, the animals will be kept under the same WD regimen or will receive WD reduced in fats and sugars (chow with 20% lard and sucrose, and water) for 3 weeks. Concomitantly, the animals will be treated with yacon root syrup (0.30 g/g of FOS) intragastically (5×/week), at 8.5 or 17 g/kg body weight, based on in the calculation of Human Equivalent Dose (HED). A glucose tolerance test will be performed, and the animals will be euthanized after this period. Alanine aminotransferase and total cholesterol will be determined in serum samples. Liver samples will be used for NAFLD activity score (HE), collagen area (Sirius red), and the caspase-3 (apoptosis), Ki67 (proliferation), CD68 (macrophages) and ±-SMA (stellate cells) will be evaluated by immunohistochemistry. The size of adipocytes (HE), mast cells (toluidine blue) and the CD68 marker will be evaluated in the AT. The morphometry of the crypts (HE), goblet cells (PAS alcian blue), and the Ki67 marker will be evaluated in the colon. The levels of malondialdehyde and the activity of the superoxide dismutase and catalase enzymes will be evaluated in both liver and AT. Metabolomics will be performed by nuclear magnetic resonance spectrometer in liver and colon content samples. The latter will be also destined to microbiome determination by pyrosequencing of 16S rRNA gene. (AU)