Investigating the Effect of Short-term Fasting on T Cell Metabolism, Function, and Phenotype in Obesity

NCT05886738 | Unknown

• 1 other identifier: H22-03605
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

The immune system is made up of many types of immune cells, each of which play a specialized role in protecting against pathogens. T cells are a crucial part of the adaptive immune system, and receive signals from the body's metabolism which tell them whether they should become activated to respond to an infection or if they should stay in their resting state. In obesity, the body's metabolism shifts and these T cells become less effective at protecting against infection and instead start to increase inflammation which is involved in obesity-related health conditions. The investigators are conducting this study because the investigators are interested in understanding how fasting, which will alter the metabolic signals that T cells receive, might impact the types of T cells that are present and how they respond to activating signals. Additionally, the investigators are interested in understanding if these responses differ between T cells from individuals with obesity versus lean individuals.

Conditions

Obesity; Fasting; T-Cell Dysfunction

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the rate of T cell fat-supported oxidative mitochondrial respiration assessed by Oroboros O2K after 48 hours of fasting

  T cell respiration will be characterized in inactivated and activated T cells collected at baseline and after 48 hours of fasting. Inactivated T cells will be assessed immediately following isolation. Activated T cells will be assessed after culturing with CD3/CD28 for 24 hours.

  Baseline and 48 hours

Secondary Outcomes (2)

• Change from baseline in the frequency (%) of T cell subsets assessed by multi-colour flow cytometry

  Baseline and 48 hours

• Change from baseline in the rate of T cell proliferation assessed by cell number

  Baseline and 48 hours

Study Arms (2)

Obese

EXPERIMENTAL

Individuals with obesity will be recruited. Obesity will be defined as having a body mass index \>= 30 kg/m2 or a waist circumference of \> 88cm (females) or \>102 cm (males).

Other: Fasting

Lean

ACTIVE COMPARATOR

Lean individuals will be recruited and will act as the reference arm such that we will compare responses of individuals with obesity to the lean group. This group will be defined as having a BMI between 18.5-24.9 kg/m2 and a waist circumference of less than 88 cm (females) or 102 cm (males)

Other: Fasting

Interventions

Fasting OTHER

Obese and lean groups will fast for 48 hours, followed by a 3-hour refeeding period.

Lean; Obese

Eligibility Criteria

• Age: 19 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• are 19-69 years of age, and
• have body mass index (BMI) of between 18.5 and 24.9 kg/m2 and a waist circumference of less than 88 cm (females) or 102 cm (males), or
• have a BMI over 30 kg/m2 or a waist circumference of more than 88 cm (females) or 102 cm (males)
• can read and understand English

You may not qualify if:

• Have a diagnosed autoimmune or inflammatory disease
• Have had a cancer diagnosis and/or treatment within the last 5 years
• Have diagnosed type 1 or 2 diabetes
• Have a history of cardiovascular events (e.g., heart attack, stroke)
• Are taking glucose-lowering or thyroid medications
• Are currently taking ketone supplements, practice intermittent fasting, following a ketogenic diet, or are actively trying to lose or gain weight (more than 4 kg weight loss or gain in the last month)
• Are accumulating 150 minutes or more of moderate-to-vigorous physical activity per week, or are participating in moderate-to-vigorous physical activity on 3 or more days per week
• Smoke cigarettes or cannot refrain from smoking/using cannabis for the duration of the study
• Are currently pregnant

Sponsors & Collaborators

• University of British Columbia: lead

Related Publications (1)

• Neudorf H, Sandilands RE, Ursel S, Shaba H, Barg D, Tsusaka T, Moya-Garzon MD, Vaz E, Schimweg P, Goldberg EL, Long JZ, Kruger K, Islam H, Little JP. Altered immunometabolic response to fasting in humans living with obesity. iScience. 2025 Jun 11;28(7):112872. doi: 10.1016/j.isci.2025.112872. eCollection 2025 Jul 18.

  PMID: 40662191 DERIVED

MeSH Terms

Conditions

Obesity; Fasting

Interventions

Angptl4 protein, mouse

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Feeding Behavior; Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Participants will be fasting for 48 hours so it will not be possible to mask the intervention
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Jonathan Little, Principle Investigator, Professor

Study Record Dates

• First Submitted: May 12, 2023
• First Posted: June 2, 2023
• Study Start: June 1, 2023
• Primary Completion: August 30, 2023
• Study Completion: August 30, 2023
• Last Updated: June 2, 2023

Record last verified: 2023-05