BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions

Area of Science:

• Metabolic research
• Endocrinology
• Adipose tissue biology

Background:

• Thermogenesis in brown adipose tissue (BAT) is crucial for energy balance in mammals.
• Bone morphogenetic proteins (BMPs) are known regulators of adipogenesis.
• The specific role of BMPs in regulating mature BAT thermogenesis remains largely unexplored.

Purpose of the Study:

• To investigate the role of Bone Morphogenetic Protein 8B (BMP8B) in the direct regulation of thermogenesis in brown adipose tissue.
• To elucidate the molecular mechanisms by which BMP8B influences energy expenditure and metabolic rate.
• To examine the impact of BMP8B on hypothalamic signaling pathways involved in appetite and energy homeostasis.

Main Methods:

• Utilized Bmp8b knockout (Bmp8b(-/-)) mouse models to assess thermogenic and metabolic phenotypes.
• Investigated the effects of BMP8B on noradrenaline-induced responses in mature BAT, including signaling pathways (p38MAPK/CREB) and lipase activity.
• Analyzed neuropeptide levels and AMP-activated protein kinase (AMPK) phosphorylation in the hypothalamus of Bmp8b(-/-) mice.
• Administered central BMP8B treatment to assess its effects on BAT sympathetic activation and hypothalamic AMPK status.

Main Results:

• Bmp8b(-/-) mice exhibited impaired BAT thermogenesis, reduced metabolic rate, and significant weight gain despite reduced food intake (hypophagia).
• BMP8B induction in mature BAT enhanced noradrenaline response via p38MAPK/CREB signaling and increased lipase activity.
• Bmp8b(-/-) mice showed altered hypothalamic neuropeptide profiles and reduced AMPK phosphorylation, suggesting an anorexigenic state.
• Central BMP8B administration stimulated BAT sympathetic activity, dependent on hypothalamic AMPK signaling.

Conclusions:

• BMP8B is identified as a key thermogenic protein that directly regulates energy expenditure in brown adipose tissue.
• BMP8B acts in concert with hypothalamic AMPK to maintain energy balance, influencing both energy dissipation and appetite.
• BMP8B presents a potential therapeutic target for increasing energy expenditure and combating metabolic diseases like obesity.