De Novo Lipogenesis and Insulin Sensitivity in Obese

NCT04260542 | Completed

• 1 other identifier: NV19-01-00263
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief 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

Keywords

adipose tissue; insulin resistance; obesity; ketogenic diet; de novo lipogenesis

Outcome Measures

Primary Outcomes (2)

• Insulin sensitivity

  Change in insulin sensitivity index (ΔiAUC insulin/ΔiAUC glucose from OGTT)

  through study completion, an average of 1 year

• De Novo Lipogenesis in adipose tissue

  Change in mRNA expression of lipogenic genes and by targeted and non-targeted lipid analysis (ΔCT)

  through study completion, an average of 1 year

Secondary Outcomes (1)

• gene expression profiling of adipose tissue

  through study completion, an average of 1 year

Other Outcomes (2)

• Exploratory outcome into adipose tissue lipolysis

  through study completion, an average of 1 year

• Exploratory outcome into liver lipogenesis

  through study completion, an average of 1 year

Study Arms (3)

FAST Lean

ACTIVE COMPARATOR

Short-term fasting (FAST), comparator group of lean subjects

Behavioral: Fasting/refeeding

FAST Obese

EXPERIMENTAL

Short-term fasting (FAST), experimental group of obese subjects

Behavioral: Fasting/refeeding

KETO Obese

EXPERIMENTAL

Medium-term ketogenic diet intervention (KETO), experimental group of obese subjects

Behavioral: Ketogenic diet/ fasting

Interventions

Fasting/refeeding BEHAVIORAL

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).

Also known as: FAST lean

FAST Lean

Ketogenic diet/ fasting BEHAVIORAL

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).

Also known as: KETO obese

KETO Obese

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• sedentary premenopausal women
• lean (n=20-25, age 25-40 years, BMI 20-25 kg/m2)
• obese (n=20-25, age 25-40 years, BMI 30-40 kg/m)

You may not qualify if:

• diagnosed cancer
• diabetes (T1DM and T2DM)
• liver and renal diseases
• major cardiovascular event
• bariatric surgery
• allergy to lidocaine
• positive serology for hepatitis (B and C) and HIV
• smoking above 10 cigarettes/day, alcohol consumption above 66g/day
• sleep apnea
• poor venous status
• weight-change more than 3kg in last 3 months
• untreated hyper- or hypo-thyroidism
• long term use of medication and/or steroids
• shift workers and individuals with abnormal sleep/wake pattern

Sponsors & Collaborators

• Charles University, Czech Republic: lead
• Faculty Hospital Kralovske Vinohrady: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (2)

Charles University

Prague, 100 00, Czechia

Location

Faculty Hospital Kralovske Vinohrady

Prague, Czechia

Location

MeSH Terms

Conditions

Insulin Resistance; Obesity

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Michaela Siklova, PhD

  Charles University, Czech Republic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy head of adipose tissue physiology lab

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: February 7, 2020
• Study Start: May 1, 2019
• Primary Completion: March 11, 2022
• Study Completion: March 11, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

CZ (2)