Circadian Rhythms in Human Adipose

Circadian Regulation of Human Adipose Tissue Metabolism

The goal of this study is to understand the underlying circadian rhythms in subcutaneous adipose tissue of humans with our without continuous feeding and how these are altered in people who have obesity.

Study Overview

• Status: Recruiting
• Conditions: Obesity, Abdominal; Feeding Patterns
• Intervention / Treatment: Other: Continuous Feeding; Other: Intermittent feeding

Detailed Description

This proposal will address 3 main aims: 1) Determine the impact of endogenous AT circadian rhythms on AT function independent of diurnal nutrient delivery in humans, 2) determine the impact of central obesity on adipocyte circadian clock, and 3) establish for the first-time in vivo human adipocyte specific cistrome of the core circadian clock transcription factors, BMAL1 and CLOCK. In order to understand whether adipocytes have intrinsic circadian clock entrainment that is separate from food entrainment, we will compare rhythmicity of AT of lean volunteers studied under continuous vs. intermittent feeding paradigms. 20 normal weight adults (M/F= 10/10, split evenly between feeding groups) will be randomized to receive either "continuous" (CONT) feedings via a nasogastric (NG) feeding tube or receive 3 meals a day for the "intermittent" (INTER) study, also delivered via NG tube. The screening prior to the inpatient study visit will include vital signs, height, weight, hip/waist/neck circumference, body composition (DEXA scan) plasma lipid profile and fasting glucose. Potential volunteers will fill out questionnaires to exclude sleep disorders and assure normal sleep habits. For 3 days prior to and during the inpatient study, volunteers will be required to wear an Actiwatch 24 h/day; which objectively measures 24-hour sleep quality and quantity. (see detailed methodology).

For the inpatient visit, volunteers will be admitted to Mayo Clinic Clinical Research and Trials Unit (CRTU) at 1500 h where an NG tube will be placed. After baseline blood samples, the CONT feeding group will start liquid feedings (Ensure Plus®) at 1800 and continue for the next ~37 hrs. This will provide 12 h of continuous feeding before the first abdominal AT biopsies; this duration of continuous feeding abolishes the wide fluctuations in plasma insulin that occurs with normal meals and will avoid the progressive lipolytic response that would occur if fasting were used as the experimental design. FFA during isocaloric, continuous feeding is well within normal intraday variability. Participants randomized to INTER will receive 1/3rd of their daily energy needs at each "meal" via NG tube. These feedings will be given at 1800 h and 3 separate meals the following day. Participants will undergo measures of resting energy expenditure following the overnight period to appropriately interpret FFA Ra data.

To avoid retrieving AT sample from previously disrupted biopsy sites, every participant will be limited to 4 abdominal adipose tissue biopsies (1 per abdominal quadrant). To ensure a full 24 hours of data, all participants will have biopsies at: 0600, 1800, and 0600 the next day, half of participants will have a biopsy at 1200 and the other half at 2400. This hybrid (linked-cross sectional) will allow us to sample in series from multiple people and then create sample group means to account for disparate biopsy numbers. We are sampling from abdominal adipose tissue as this is the primary source of circulating FFA in humans and thus is the most likely for us to ascertain regulation of lipolysis proteins.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kelli A Lytle, PhD; Phone Number: 507-255-1488; Email: lytle.kelli@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55901
      • Recruiting
      • Mayo Clinic
      • Contact: Kelli A Lytle, PhD; Phone Number: 503-255-1488; Email: lytle.kelli@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI 20-25 kg/m2 or 30-37 kg/m2
• For participants with obesity a waist-to-hip ratio of ≥0.95 in males and ≥0.90 in females.
• sedentary
• females: non pregnant or breastfeeding
• ability to provide written informed consent and follow study instructions

Exclusion Criteria:

• History of mediations that impact adipocyte/lipid metabolism
• smoking
• insomnia
• sleep apnea
• sleep medication use
• employment in night or shift work
• extreme chronotypes
• Allergy to lidocaine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Normal weight participants	Other: Continuous Feeding; Participants will receive 24-hour continuous feeds through an NG tube; Other: Intermittent feeding; Participants will receive 3 boluses of feeding per day at regular meal times through an NG tube to mimic normal meals.
Active Comparator: Participants with obesity	Other: Continuous Feeding; Participants will receive 24-hour continuous feeds through an NG tube; Other: Intermittent feeding; Participants will receive 3 boluses of feeding per day at regular meal times through an NG tube to mimic normal meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rhythmicity of circadian clock mRNA in adipose tissue	Genes from RNA-seq analysis will be defined as statistically rhythmic.	24 hour

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 21, 2025
• First Posted (Actual): March 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: obesity; adipose tissue; circadian rhythms; feeding pattern
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Behavior, Animal; Obesity; Obesity, Abdominal; Feeding Behavior
• Other Study ID Numbers: 20-004280; K01DK140206 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No