The Effects of Acute Weight Gain and Acute Calorie Deprivation on Marrow Adipose Tissue

Marrow adipocytes have been identified as a component of the bone marrow micro-environment. Evidence exists suggesting that marrow fat plays an important physiologic role in both bone mineral and energy metabolism in humans. The investigators will study the effects of acute weight gain and acute nutritional deprivation on energy homeostasis and bone mineral metabolism by examining marrow adiposity, peripheral fat depots and bone microarchitecture.

The study will include two ten day inpatient study visits. Participants will eat a high calorie diet for 10 days, followed by a 13-18 day stabilization period at home, and then return for a ten day fast.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: High calorie diet; Other: Fasting

Detailed Description

Marrow adipocytes have been identified as a component of the bone marrow micro-environment. Evidence exists suggesting that marrow fat plays an important physiologic role in both bone mineral and energy metabolism in humans. Studies have shown that nutritional status, particularly body fat distribution, may be important in marrow fat. For example, anorexia nervosa, a state of low body fat, is associated with elevated marrow adiposity and low bone mineral density. However, it is not known whether this is in direct response to nutritional deprivation or other hormonal changes that occur in anorexia nervosa. Drugs known to cause adipose redistribution and associated with low bone mass, such as the thiazolidinediones and glucocorticoids, have also been shown to stimulate the accumulation of marrow adipocytes. Therefore, the relationship between bone marrow fat, bone mass, body fat depots and their hormone regulators is a dynamic one and not yet well understood. Although studies have shown an inverse relationship between high marrow adiposity and low bone mineral density (BMD), the physiologic role of marrow adipose tissue has not been defined nor its relationship to hormonal factors in humans. A role for marrow adipose tissue (MAT) in mineral and energy metabolism is further supported by the fact that a number of pathologic states are associated with increased marrow adiposity. Visceral adipose tissue, intramyocellular lipids (IMCL), intrahepatic lipids (IHL) and serum triglycerides, all of which are elevated in obesity, are also positive predictors of MAT, but whether acute weight gain in humans results in elevated marrow adiposity is unknown. Therefore observing changes in marrow fat during acute weight gain and acute nutritional deprivation will further the understanding of the role of marrow adiposity in energy homeostasis. While it is known that markers of bone formation dramatically decrease after only 4 days of fasting, it is not known how quickly marrow fat can change in response to physiologic cues. In a rat model, increases in marrow fat were observed after 14 days in space suggesting that changes in marrow adiposity may occur acutely in the human model as well.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusettes General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women, ages 21-45 years
2. 101-120% of ideal body weight as defined by the 1983 Metropolitan Life Insurance Height and Weight Tables
3. Normal thyroid function
4. Regular menses (women) - Female subjects will start the study within 1 week of Day 1 of their menstrual period
5. Normal transaminase levels (AST/ALT)

Exclusion Criteria:

1. Any disease known to affect bone metabolism, including untreated thyroid dysfunction, Cushing's syndrome, or renal failure
2. Any medication known to affect bone metabolism -- including systemic steroids or immunosuppressants -- within three months of the study, excluding estrogen and progestins. Patients receiving depot medroxyprogesterone (Depo-Provera) will be excluded from participating for six months after their last injections. Bisphosphonates must have been discontinued for at least one year before participation
3. Serum potassium <3.0 meq/L
4. History of eating disorder
5. Pregnant and/or breastfeeding (women)
6. Diabetes mellitus
7. Active substance abuse, including alcohol
8. Contraindications to MRI: cardiac pacemaker, metal implants, claustrophobia
9. History of chemotherapy or radiation therapy
10. History of a bleeding disorder or use of anti-platelet medications
11. Allergy to allopurinol
12. The study physician feels that the subject may not be able to safely complete the study or may place themselves at risk by undergoing the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 10 day overfeeding/fasting; 10 day high calorie diet followed by a 10 day fast	Other: High calorie diet; High calorie diet for 10 days; Other: Fasting; 10 day fast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Marrow adiposity will be measured using magnetic resonance spectroscopy	Marrow adipose tissue measurement of the spine and hip	Change from baseline marrow adipose tissue after high-calorie diet and after fast (35 days)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Anne Klibanski, MD, MGH/Harvard Medical School

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: December 30, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: 2015P000624