Thought to Be Degeneration Traces in Brain Cells... 'Simultaneous Regulation of Bone and Metabolism'

Confirmation of the Role of Hypothalamic Primary Cilia in Animal (Mouse) Models
Proposing Mechanisms for Concurrent Regulation of Metabolism Including Obesity and Bone Diseases

Data indicating the disruption of energy metabolism homeostasis upon primary cilium loss in hypothalamic ventromedial nucleus SF-1 neurons.

[Asia Economy Reporter Junho Hwang] The function of primary cilia present in the hypothalamic neurons of the human brain has been revealed by a domestic research team. It was confirmed that primary cilia, previously dismissed as vestigial organs, are essential cellular organelles involved in energy metabolism and bone formation. The research team expects this to provide important clues for drug development targeting bone diseases (such as osteoporosis) associated with metabolic disorders like obesity and diabetes in the future.

The research team led by Professor Kiwoo Kim of Yonsei University College of Dentistry disclosed this function of primary cilia, and the related paper was published in the Journal of Clinical Investigation on the 21st.

The Secret of Primary Cilia, Once Thought to Be Vestigial Organs

Changes in Bone Homeostasis Due to Primary Cilia Deficiency in the Hypothalamic Arcuate Nucleus

Unlike motile cilia found in the nasal mucosa and lung surfaces, primary cilia are non-motile microtubules known as receptors that transmit various sensory signals in sensory organs. However, through prior research, the team revealed that specific neurons (SF-1) in the ventromedial nucleus of the hypothalamus play an important role in energy metabolism, and that these neurons have unusually long primary cilia on their surfaces. In addition, this study investigated the impact of primary cilia on the regulation of energy metabolism. They constructed a knockout animal model in which primary cilia were not formed in SF-1 neurons to observe the results.

The research team reported that the knockout mouse model lacking primary cilia exhibited severe obesity. They also found that this was due to energy metabolism suppression caused by reduced oxygen consumption and defects in energy expenditure. In fact, blood norepinephrine, a measure of sympathetic nervous system activity that autonomously induces bodily tension, was significantly lower in the mouse model. The team explained that the loss of primary cilia reduced sympathetic nervous system activity, which decreased sensitivity to the appetite-suppressing hormone leptin, leading to overeating.

Essential for Metabolism and Bone Homeostasis

A summarized illustration of the research. Functional impairment of primary cilia not only leads to decreased sympathetic nervous system activity but also causes dysfunction of leptin, a hormone that regulates energy balance, ultimately resulting in obesity due to energy imbalance. Along with this, the reduced sympathetic nervous system activity disrupts the balance of bone metabolism, leading to changes in bone density.

The research team also observed increased bone density in the primary cilia-deficient mice. While osteoclasts, which break down bone, decreased, the rate of bone formation accelerated. This was a result of disrupted bone homeostasis due to autonomic nervous system regulation abnormalities, independent of obesity.

Based on these results showing that primary cilia involved in sympathetic nervous system activity are essential for maintaining energy metabolism and bone homeostasis, the research team announced plans for follow-up studies on factors involved in the activation and length maintenance of primary cilia.

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