Regulation and Function of Adipose Tissue Remodeling

  • BAT HE
  • IF
  • BAT EM

White adipose tissue

The excess of fat accumulation in the white adipose tissue (WAT) leads to obesity, which is a major risk factor for many diseases, including type 2 diabetes, hypertension, heart disease, and some types of cancers. In obesity, WAT undergoes the hypertrophic (i.e. increased adipose size) and hyperplasic (i.e. increased adipose number) expansion through different mechanisms. We are interested in identifying genes and pathways that control different forms of WAT remodeling in obesity and aging.

Brown and beige adipose tissues

Prevention and treatment of obesity are difficult, largely because changes in food intake and body weight are associated with compensatory changes in energy expenditure, which keep body weight at the original “set point”. In other words, we need to increase energy expenditure, in addition to lifestyle interventions and medications, to treat obesity. In contrast to classic WAT, brown adipose tissue (BAT) and “brown-like” beige adipocytes in WAT burn fat and dissipate chemical energy as heat (thermogenesis), through uncoupling protein 1 (UCP1)-dependent and -independent mechanisms. The potential of brown and beige adipocytes as anti-obesity targets attracts extensive interest (Fig. 1).   

1) To identify extrinsic and intrinsic factors that govern the thermogenic program. In humans, the prevalence and activity of BAT strikingly decrease with age and in obesity. We are currently using rabbits and mice as models to understand how BAT remodels in life and whether it can be reactivated in obesity.

2) To understand how thermogenic adipocytes modulate systemic metabolism. BAT secretes adipokines, aka “batokines”, to either control the thermogenic program in autocrine and paracrine manners or modulate systemic glucose and lipid metabolism as hormones. We are interested in identifying and characterizing novel batokines.

Bone marrow adipose tissue

Bone marrow adipose tissue (MAT) is the third major adipose depot in the body and its function is just beginning to be revealed. Marrow adipocytes arise from skeletal stem cells within the marrow stroma. The mass of constitutive MAT (cMAT) that exists in the most distal portion of the tibia and tail vertebrae is relative stable, while regulated MAT (rMAT) found in the proximal skeletal sites expands in conditions like obesity, diabetes, caloric restriction, and aging. There are tripartite interactions between MAT, bone, and hematopoiesis, yet a mechanistic understanding has not been fully achieved. We aim to understand how MAT remodels upon metabolic stresses and whether MAT acts as a niche for hematopoietic stem and progenitor cells.

Related publications:

1. Zhang Z, Huang Z, Ong B, Sahu C, Zeng H, Ruan HB. (2019). Bone marrow adipose tissue-derived stem cell factor mediates metabolic regulation of hematopoiesis. Haematologica. 104(9):1731-1743. 
2. Wang Q, Tang J, Jiang S, Huang Z, Song A, Hou S, Gao X, Ruan HB. (2018). Inhibition of PPARγ, adipogenesis and insulin sensitivity by MAGED1. Journal of Endocrinology. 239(2): 167-180.
3. Ruan HB, Dietrich MO, Liu ZW, Zimmer MR, Li MD, Singh JP, Zhang K, Yin R, Wu J, Horvath TL, Yang X. (2014). O-GlcNAc transferase enables AgRP neurons to suppress browning of white fat. Cell. 159(2): 306-317.
4. Huang Z, Ruan HB, Xian L, Chen W, Jiang S, Song A, Wang Q, Shi P, Gu X, Gao X. (2014) The stem cell factor/Kit signaling pathway regulates mitochondrial function and energy expenditure. Nature Communications. 5:4282.

Fig. 1: A trio of fat.