Li Lab

Our lab investigates how the gut, bone, heart, and bone-resident cells interact—and how these communication networks shape overall metabolic and endocrine health.

Model of how gastric secretory factors contribute to VSG-caused bone loss.

Gastric Endocrine Functions in Skeletal Homeostasis

Bariatric surgery-associated skeletal complications have been observed since the early 1990s, and lead to up to two-fold increase in fracture risk. The most common bariatric surgery is vertical sleeve gastrectomy (VSG), which leads to ~3-7% bone loss at the axial skeleton after 6-24 months. Current clinical management includes bone mineral density assessments, consumption of adequate dietary calcium, vitamin D, and protein, and performance of weight-bearing exercise. These countermeasures minimize, but do not fully prevent bone loss secondary to bariatric surgery. A better mechanistic understanding of bone loss associated with bariatric surgery is necessary to properly design and evaluate preventive and therapeutic strategies. We propose that gastric hormones contribute to bariatric surgery-induced skeletal complications. My group found gastric X/A-like cells (P/D1 cell in humans), a unique endocrine cell population, contribute to the regulation of global lipid metabolism, marrow adiposity and bone formation, suggesting a stomach-bone axis. Our goals are: 1) to determine the effects of gastric X/A-like cell-derived secretory factors on VSG-induced bone loss; and 2) to identify and characterize gastric hormones from X/A-like cells that regulate skeletal homeostasis.

Schematic of the local functions of BMAT in bone and hematopoietic metabolism.

Bone Marrow Adipocytes: Key Modulators of the Local Bone Marrow Niche

Bone marrow adipocytes (BMAds), once considered inert fat storage, are now recognized as a dynamic endocrine and signaling organ. As a crucial component of the bone marrow niche, BMAds reside within a complex tissue that houses a multitude of other cell types, including osteoblasts, osteoclasts, and various hematopoietic and immune cells. Their unique location gives them distinct characteristics from other fat depots, and their function remains a subject of intense research. Using a BMAd-specific mouse model that allows for highly selective genetic manipulation. we are exploring the specific substances through which BMAds regulate the osteogenic potential of bone marrow stromal cells by integrating large-scale proteomic, transcriptomic, and lipidomic datasets.