Metabolic characterization of adipocytes in response to serum of rodents subjected to dietary restriction

Author(s)

Raissa Guimarães Ludwig

• Document type: Master's Dissertation
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2018-02-21

Examining board members

Marciane Milanski; Dora Maria Grassi Kassisse

• Advisor: Marcelo Alves da Silva Mori

Abstract

The prevalence of obesity has been growing worldwide alongside its comorbidities. Current anti-obesity therapies appear to be poorly efficient, especially on the long-term, and are associated with significant side effects. There are two ways to lose weight: by decreasing energy intake or increasing energy expenditure. One way to increase energy expenditure in mammals is through the stimulation of brown/beige adipocytes and the increase in their function. This phenomenon usually correlates with high levels of UCP1 expression and activity. Some conditions capable of regulating UCP1 expression and function have already been described. Among them, there is chronic cold exposure, exercise, an enriched social environment, and cancer cachexia. These conditions act through cell autonomous mechanisms, such as by regulating transcription factors in preadipocytes or adipocytes, and cell non-autonomous mechanisms, such as by signaling through hormones and other circulating molecules. The study and understanding of the circulating molecules that act in adipose tissue to increase its brown/beige characteristics is essential for the development of more efficient and secure pharmacological strategies that could help to mitigate the global scenario of obesity. We observed, based on our preliminary results, that serum of mice subjected to dietary restriction modulates the expression of Ucp1 in vitro in mouse adipocytes derived from brown adipose tissue. This seems to be due to one or more circulating molecules present in the serum of ad libitum-fed individuals that induce Ucp1 in a dose-dependent manner. These molecules are absent or very low in serum of DR-subjected individuals. Even though no functional effect was observed in differentiated 9B cells, it seems to stimulate Ucp1 transcription or to stabilize its transcript. Interestingly, this effect can be reproduced using serum of rats indicating species conservation. These circulating molecules are likely proteins or protein-dependent molecules and do not act through beta-adrenergic pathway. This/these molecule(s) may bring insights into the development of new drugs to combat obesity (AU)

• FAPESP's process: 15/20822-0 - Metabolic characterization of adipocytes in response to serum of rodents subjected to dietary restriction
• Grantee: Raissa Guimarães Ludwig
• Support Opportunities: Scholarships in Brazil - Master