Thyroid hormone excess secondary to global type 3 deiodinase (DIO3) deficiency leads to increased locomotor activity and reduced adiposity, but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity. To distinguish the underlying contributions to the energy balance phenotype of DIO3 deficiency, we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin (POMC)-expressing cells via cell-specific DIO3 inactivation. These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression, hyperphagia, and increased activity in brown adipose tissue, with adiposity and serum levels of leptin and thyroid hormones remained normal. These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a (BMPR1A), which has been shown to cause similar phenotypes when inactivated in POMC-expressing cells. Our results indicate that developmental overexposure to thyroid hormone in POMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.
Keyphrases
- induced apoptosis
- adipose tissue
- cell cycle arrest
- insulin resistance
- poor prognosis
- pulmonary arterial hypertension
- high fat diet induced
- public health
- oxidative stress
- type diabetes
- signaling pathway
- endoplasmic reticulum stress
- stem cells
- binding protein
- metabolic syndrome
- cell death
- single cell
- long non coding rna
- mesenchymal stem cells
- spinal cord injury
- physical activity
- pulmonary hypertension
- bone marrow
- radiation therapy
- weight gain
- drug delivery
- pi k akt
- wild type
- bone loss