Study of the metabolic and molecular changes involved in caloric restriction and the hypoprotein diet in humans

Author(s)

Rafael Ferraz Bannitz

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2021-06-25

Examining board members

Maria Cristina Foss de Freitas; Luiz Osório Silveira Leiria; Luiz Carlos Carvalho Navegantes; Lício Augusto Velloso

• Advisor: Maria Cristina Foss de Freitas

Abstract

In recent decades, obesity has become an important public health problem worldwide, resulting in the increased prevalence of chronic diseases, generally associated with obesity, such as coronary heart disease and Type 2 diabetes mellitus. Many studies are carried out in an attempt to design interventions that can block or minimize obesity-induced metabolic diseases, especially Type 2 diabetes. Caloric restriction (CR) reduces adiposity and improves metabolism in patients with one or more symptoms of the metabolic syndrome. However, it is not known whether the benefits of CR in humans are mediated by caloric or nutrient restriction. This study was carried out to identify whether the isocaloric diet with protein restriction (PR) is able to confer the beneficial effects of CR in patients with metabolic syndrome. We subjected 21 individuals diagnosed with metabolic syndrome to shortterm (ie, 27 days) caloric restriction (CR; n = 11) or isocaloric diet with protein restriction (PR; n = 10) and compared the metabolic and molecular results of the interventions. Like CR, PR promoted weight loss due to reduced adiposity and reduced blood glucose, lipid levels and blood pressure in these individuals. We observed a reduction in insulin resistance, by an increase of 62.3% and 93.1% in the glucose infusion rate during the hyperinsulinemic euglycemic clamp and a reduction of 61.1% and 56.6% in the HOMA-IR, for CR and PR respectively. Gene expression signatures in subcutaneous adipose tissue (SAT) were significantly modified in samples from individuals in the CR and PR groups. We observed an increase in mRNA expression mainly in genes related to adipocyte metabolic function (Adipoq) and presence of nutrients (AMPK, GCN2 and SIRT1). We did not find significant changes in the composition of the gut microbiome after PR, although 12 species, mainly Firmicutes, changed considerably. Our data suggest that reducing protein intake with a slight increase in carbohydrate intake to maintain dietary isocaloric balance is sufficient to improve metabolic control. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has greater potential to be used as an adjunctive therapy in the treatment of metabolic syndrome. (AU)

• FAPESP's process: 15/12133-0 - Study of metabolic and molecular alterations involved in caloric restriction and hypoproteic diet in humans
• Grantee: Rafael Ferraz Bannitz
• Support Opportunities: Scholarships in Brazil - Doctorate