Bone Marrow Adipose Tissue in Relation to Bone and Energy Metabolism in Obesity and Type 2 Diabetes Mellitus

Summary

This interventional study is part of a broader research project entitled "Bone Marrow Adipose Tissue in Relation to Bone and Energy Metabolism in Obesity and Type 2 Diabetes Mellitus." The broader project includes both a cross-sectional study evaluating bone marrow adipose tissue and bone marrow mesenchymal stem cells in people with different metabolic and bone disorders and the present dietary intervention study. The interventional study investigates whether caloric restriction changes bone marrow adipose tissue, bone health, whole-body metabolism, and the molecular and cellular characteristics of bone marrow mesenchymal stem cells in obese non-diabetic premenopausal women. A group of lean healthy premenopausal women will serve as a comparison group. Participants in the intervention group will undergo an eight-week formula-based very-low-calorie diet using Cambridge Weight Plan products, providing approximately 2.5-3.35 MJ (600-800 kcal) per day, followed by a dietary weight-maintenance phase. Participants will receive nutritional counselling, and dietary adherence, body weight, physical activity, and clinical status will be monitored during scheduled study visits. Clinical and laboratory assessments will be conducted at baseline and after 2, 6, and 12 months. Assessments will include magnetic resonance imaging and proton magnetic resonance spectroscopy of the lumbar spine to measure the amount and lipid composition of vertebral bone marrow adipose tissue. Bone mineral density and body composition will be measured using dual-energy X-ray absorptiometry, with particular attention to bone mineral density at the total hip and femoral neck. Additional measurements will include body weight, waist and hip circumference, body composition, physical activity, and fasting blood tests evaluating bone turnover, glucose and lipid metabolism, inflammatory markers, hormones, and adipokines. Bone marrow aspirates and abdominal subcutaneous adipose tissue biopsies will be obtained at baseline and after six months. Bone marrow-derived and adipose tissue-derived mesenchymal stem cells will be examined for changes in cellular composition, gene-expression profiles, metabolic activity, oxidative stress, differentiation capacity, and senescence-related characteristics. Single-cell RNA sequencing will be used to characterize specific bone marrow mesenchymal stem cell subpopulations. Bone marrow plasma and other biological samples will also undergo metabolomic, lipidomic, and proteomic profiling using high-resolution mass spectrometry. These analyses will be used to identify extracellular molecules and molecular patterns associated with glucose and lipid metabolism, inflammation, cellular senescence, and the response to caloric restriction. The study aims to determine whether diet-induced weight loss can improve the bone marrow microenvironment and modify vertebral bone marrow fat, bone parameters, and the metabolic and senescent phenotype of mesenchymal stem cells. The findings may help identify imaging, cellular, and molecular markers of obesity-related bone fragility.

Eligibility

Interventional Study: Effect of Caloric Restriction on BMAT/BM-MSCs Phenotype

Inclusion Criteria:

* Premenopausal women and age-eligible men assigned to either the obese intervention group or the lean control group
* Obese intervention group:
* Body mass index (BMI) of 30-42 kg/m²
* Fasting plasma glucose less than 6.4 mmol/L
* Age 25-55 years
* Lean control group:
* BMI of 19-25 kg/m²
* Fasting plasma glucose less than 6.4 mmol/L
* Age 25-50 years

Exclusion Criteria:

* Diabetes mellitus
* Secondary osteoporosis
* History of severe neuropathic disease
* Hyperparathyroidism
* Hyperthyroidism
* Immobilization
* Alcoholism
* Chronic gastrointestinal disease
* Significant chronic renal impairment, including any of the following:
* Chronic kidney disease
* Serum creatinine greater than 110 µmol/L
* Estimated glomerular filtration rate (eGFR) less than 1 mL/s/1.73 m²
* Proteinuria
* Diabetic nephropathy
* Chronic hepatic impairment
* Unstable cardiovascular disease
* Uncontrolled hypertension
* Current or recent use of any of the following medications:
* Bisphosphonates
* Estrogen
* Denosumab
* Gonadotropin-releasing hormone (GnRH) analogs
* Glucocorticoids at a dose equivalent to at least 5 mg of prednisone daily for at least 1 month
* Phenytoin
* Thiazolidinediones
* Insulin
* Adrenal or anabolic steroids
* Anticonvulsants
* Anticoagulants
* Pharmacological doses of vitamin D or vitamin A supplements
* Contraindications to magnetic resonance imaging (MRI), including:
* Pacemaker
* Metallic implants incompatible with MRI
* Claustrophobia

Conditions3

Browse More Trials