Pilot Study of Isocaloric Time Restricted Eating on Ketone Metabolism and Immunoregulation

Description

Study Description:

Intermittent fasting confers anti-inflammatory effects, although underlying metabolic mechanisms are poorly defined. This pilot study will explore ketone bodies as a mediator of inflammation in response to time restricted eating (TRE-6-hr feeding/18-hr fast) without caloric restriction compared to a more conventional dietary regimen (12-hr feeding/12-hr fast) in women classified as obese and lean.

Objectives:

Primary Aim 1: Quantify ketone body (beta-OHB) whole-body turnover after short-term early 6-hr TRE compared to a conventional 12-hr dietary regimen in women.

Primary Aim 2: Quantify CD4+ T cell responses after short-term early 6-hr TRE compared to a conventional 12-hr dietary regimen in women.

Secondary Aim 1: Determine metabolic response to short-term early 6-hr TRE in lean women vs women with obesity.

Secondary Aim 2: Determine immunomodulatory effects of short-term early 6-hr TRE in lean women vs women with obesity.

Exploratory Aim 1: Evaluate ketone body, hormonal, and cardiometabolic responses after short-term early 6-hr TRE compared to a conventional 12-hr dietary regimen in women classified as lean and with obesity.

Exploratory Aim 2: Evaluate effects of short-term early 6-hr TRE on perceived appetite, stress, and gastrointestinal symptoms.

Endpoints:

Primary:

1. Change from admission day 0 in ketone body (beta-OHB) rate of appearance (Ra) after three days of 6-hr TRE
2. Change from admission in CD4+ T cell responsiveness (Th17 polarization) after three days of 6-hr TRE

Secondary:

1. Change from admission day 0 in post-absorptive glucose Ra quantified using [6,6-2H2]glucose (intravenous) after three days 6- hr TRE
2. Change from admission day 0 in ketone body Ra in lean vs. obese women after three days 6-hr TRE
3. CD4+ T cell responsiveness (Th17 polarization) in lean vs. obese women after three days 6-hr TRE
4. Evaluation of ketone biology in isolated CD4+ T cells, using biochemical analysis and analysis of metabolic reprograming at the gene regulatory level

Exploratory:

1. Circulating ketone body concentrations at admission day 0 and after 3 days of TRE
2. Hormonal mediators of metabolic status (morning cortisol, fasting insulin and glucagon/incretins, thyroid hormones, sex hormone binding globulin, anti-mullerian hormone)
3. Cardiometabolic biomarkers (glycemic, lipid, and inflammatory; trimethylamine N-oxide [TMAO])
4. Perceived appetite, stress, and gastrointestinal symptom scores