De Novo Lipogenesis and Insulin Sensitivity in Obese

Summary

Disturbances of de novo lipogenesis (DNL) are one of the features of dysfunction of adipose tissue (AT). Disturbances of DNL play a role in development of metabolic complications of obesity. The goal of this project is to investigate novel pathways of DNL regulation. DNL will be studied during nutritional interventions in healthy and obese subjects in exposure to 2-days high carbohydrate diet preceded by a) 2-days fasting b) several weeks´ ketogenic diet. This nutritional protocol creates conditions for the study of prominent changes in DNL: suppression of DNL during fasting or ketogenic diet followed by stimulation during high-carbohydrate diet. Systemic phenotypic features and molecular indices of DNL regulation in AT will be followed during the protocols. Specific attention will be paid to newly reported pathway- hormone sensitive lipase and transcription factor ChREBP. The results will contribute to development of pharmacological approaches in the treatment of metabolic complications of obesity, targeted selectively to AT, without side effects in other tissues.

Conditions

• Insulin Resistance
• Obesity

Interventions

BEHAVIORAL

Fasting/refeeding

2-days fasting followed by 2-days of refeeding. During the fasting period the subjects will be hospitalized to control their state of health and ensure fasting compliance. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat).

BEHAVIORAL

Fasting/refeeding

2-days fasting followed by 2-days of refeeding. During the fasting period the subjects will be hospitalized to control their state of health and ensure fasting compliance. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat).

BEHAVIORAL

Ketogenic diet/ fasting

1 month of fasting-mimicking ketogenic diet and subsequent 2-days of refeeding. The subjects will be instructed by nutritional specialist to follow isocaloric ketogenic diet consisting of 6% carbohydrates, 17 % of proteins and 77% fat to cover individual energy demand. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat).

Sponsors & Collaborators

• Faculty Hospital Kralovske Vinohrady

  collaborator OTHER_GOV

• Institut National de la Santé Et de la Recherche Médicale, France

  collaborator OTHER_GOV

• Charles University, Czech Republic

  lead OTHER

Principal Investigators

• Michaela Siklova, PhD · Charles University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-05-01

Primary Completion

2022-03-11

Completion

2022-03-11

Countries

• Czechia

Study Locations