Investigation of the thermogenic and metabolic potential of the Camellia sinensis plant in obese mice - systemic repercussion of the beige phenotype.

Author(s)

Anaysa Paola Bolin

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2018-03-28

Examining board members

Rosemari Otton; Marcelo Augusto Christoffolete; William Tadeu Lara Festuccia; Lila Missae Oyama; Alice Cristina Rodrigues

• Advisor: Rosemari Otton

Abstract

The development of thermogenic/beige adipocytes in white adipose tissue (WAT) might reduce the adverse effects of obesity and could help to improve metabolic health. Certain pharmacological and nutritional agents can promote those effects by activating transcription factors or regulatory signaling pathways furthering WAT browning. As a nutritional or dietary supplement, compounds present in green tea (GT) has demonstrated remarkable correlations between energy metabolism and body weight (BW) loss, however, their potential contributions to the development of thermogenic/beige cells have been scarcely investigated. The aims of this study were to evaluate the relationship between metabolic alterations induced by an obesogenic diet and the induction of thermogenic/beige cells in GT-treated obese mice. We also evaluated the effect of a mix containing the main catechins found in GT (EGCG (2<font face = \"symbol\">mM), EGC (1<font face = \"symbol\">mM), ECG (0.6<font face = \"symbol\">mM) and EC (0.4<font face = \"symbol\">mM)) (Sigma) in a final concentration of 4<font face = \"symbol\">mM and a GT extract at 0.19%.in the induction of beige phenotype in vitro (3T3-F442A preadipocytes). Here, we show that obese-induced mice (cafeteria diet/16 weeks) that were treated with GT (500 mg/kg of BW) for 12 weeks showed a significant reduction in indicators of obesity such as BW gain, fat depots, hyperlipidemia and an increment in plasma adiponectin levels without alteration in food intake. The basal metabolic rate was increased as well as genes involved in FA oxidation, thermogenesis and beige cells markers in the subcutaneous AT of obese animals treated with GT. GT also decreased inflammation and endoplasmic reticulum stress induced by the diet and relief insulin resistance (IR). We also find that our treatment was able to induce a futile cycle through de novo lipogenesis to activate the thermogenic pathway in vivo and in vitro. The mix of catechins or the GT showed significant reduction of lipid accumulation and upregulated the expression of thermogenic markers related to FA oxidation and mitochondrial activation, as well as, oxygen consumption. The effects of GT and the mix of catechins occur in an autonomous manner and seems to be dependent on initial mechanism in adipogenesis through PPAR<font face = \"symbol\">g participation. Our study identified that the metabolic alterations caused by GT ingestion induce energetic expenditure and compromise the final commitment of adipose cell, still in the initial stages of the adipogenesis process, with modulations involving the PPAR<font face = \"symbol\">g pathway, associated to the activation of the futile cycle and induction of beige phenotype. These alterations culminate in an effective therapeutic strategy to combat obesity and its comorbidities. (AU)

• FAPESP's process: 12/20415-8 - Modulation of endoplasmic reticulum stress in adipocytes and leukocytes of mice induced to obesity and chronically treated with green tea extract (Camellia sinensis)
• Grantee: Anaysa Paola Bolin
• Support Opportunities: Scholarships in Brazil - Doctorate