Autophagy: regulating the seesaw of bone-fat balance

Boya Zhang ^1,2 Jing Cui ¹ Xu Zhang ¹ Ziyi Pan ¹ Liuyi Du ² Rongrong Ye ² Linlin Wen ² Wenhao Zhai ² Lei Huang ^1,2* Daowei Li ^1,2* Hongchen Sun ^1,2*

• ¹ Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, China
• ² Department of Oral Pathology, Hospital of Stomatology, Jilin University, Changchun, China

The interrelationship between bone and fat can be described as a seesaw in bone homeostasis, where osteogenesis and adipogenesis are in a delicate balance. Osteoblasts and adipocytes, which share a common origin, play key roles in this process. Bone-fat balance indicates osteogenesis and adipogenesis keeps a balance for concordant distribution of trabecular bone and bone marrow adipose tissue in bone, thereby leading to the balance between bone metabolism and lipid metabolism. Bone-fat balance is crucial for metabolic health, when disrupted by various factors, it can lead to bone-related metabolic diseases and systemic disorders, such as obesity, osteoporosis, and osteoarthritis. Recent research highlights the role of autophagy dysfunction in these metabolic conditions. Restoring autophagic function can help restore metabolic homeostasis and re-establish the bone-fat balance. This review explores the factors that regulate bone-fat balance, the consequences of imbalance under pathological conditions, and the potential of autophagy modulation as a therapeutic approach. We conclude that targeting autophagy presents a promising strategy for treating metabolic disorders and restoring bone-fat balance.