Microenvironmental Control of Adipocyte Fate and Function

Abstract

The properties of tissue-specific microenvironments vary widely in the human body and demonstrably influence the structure and function of many cell types. Adipocytes are no exception, responding to cues in specialized niches to perform vital metabolic and endocrine functions. The adipose microenvironment is remodeled during tissue expansion to maintain the structural and functional integrity of the tissue and disrupted remodeling in obesity contributes to the progression of metabolic syndrome, breast cancer, and other malignancies. The increasing incidence of these obesity-related diseases and the recent focus on improved in vitro models of human tissue biology underscore growing interest in the regulatory role of adipocyte microenvironments in health and disease.

Keywords: adipose development; biomechanics; extracellular matrix; metabolic disease; signal transduction; tissue engineering..

Figure 1 ∣. Regulatory Cues in the Adipocyte Niche.

The contents (yellow sphere = lipid droplet, gray triangle = nucleus, purple ovals = mitochondria, white circle = cytosol), extracellular matrix (gray lines) and surrounding cell types (gold spheres = white adipocytes, gray stars = preadipocytes, crimson tubes = capillaries, cream tubes = nerves) of a white adipocyte are depicted. Red boxes represent membrane sections where regulatory cues from the microenvironment are sensed.

Figure 2 ∣. Dynamics of integrin attachment to the extracellular matrix during adipocyte maturation.

The matrix-membrane interface is depicted in a time series spanning the transition from a preadipocyte (a) to a mature adipocyte (c). Structural support is provided by type I (100nm-10um diameter, brown banded fiber) and type VI (50nm diameter, brown beaded filament) collagen networks. Microfilaments (7nm diameter, purple) and microtubules (25 nm diameter, red) are abundant in the cytosol (pink) of preadipocytes, but are gradually displaced by the expanding lipid droplet, caged in vimentin (10nm, brown filament) (b,c). At the intermediate stage (b), the attachment of integrin alpha-5/beta-1 complexes (orange) to extracellular fibronectin (green) is replaced by alpha-6/beta-1 attachment to extracellular laminin (light blue). The membrane-type matrix metalloproteinase MT1-MMP (magenta) and other proteinases facilitate this switch by cleaving integrin attachments to fibronectin. The nucleus (blue) moves to the cell periphery and is deformed by the lipid droplet in mature adipocytes (c).