The Effects of Acute Weight Gain and Acute Calorie Deprivation on Marrow Adipose Tissue
Condition: Healthy
MeSH terms: Weight Gain
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): High calorie diet; Fasting
Intervention type(s): Other; Other
Intervention description(s): High calorie diet for 10 days; 10 day fast
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other