Excess adipose tissue leads to a myriad of diseases; however, the underlying mechanisms linking them together are just now becoming clearer. We’ll take a global view of the field of adipose tissue pathobiology - including the harmful effects of abdominal adiposity. This introduction will provide the context for new research pointing to the protective effects of lower body subcutaneous (LBSC) adipose tissue.
Epidemiological studies have identified that adipose tissue below the waistline, also known as lower body subcutaneous (LBSC) adipose tissue are associated with a decreased risk of cardiovascular disease in both men and women. In contrast, upper body subcutaneous adipose tissues (UBSC) and deeper adipose tissues (visceral, intermuscular, peri-cardial) are associated with increased CV risk. The reduced CV risk remains after adjusting for traditional cardiometabolic risk factors such as blood pressure, LDL-cholesterol, HDL-cholesterol and triglycerides.
The exact mechanism(s) responsible for the differences in adipose tissue effect are unknown. It is known that the repertoire of receptors on the surface of adipocytes is different between UBSC and LBSC. For example, Growth Hormone (GH) Receptors are increased in UBSC vs. LBSC; this is consistent with functional data in-vivo and in-vitro. The alpha adrenoreceptor repertoire is also different accounting for some of the differences in lipid flux under physiological conditions. Similarly, the repertoire of estrogen and progesterone receptors is different. Together, these differences explain how the hormonal milieu (sex steroids, cortisol, GH) can shape the deposition of energy in LBSC vs. UBSC adipose tissue and influence lipid dynamics. A key alternative hypothesis is that LBSC might secrete a beneficial factor to prevent insulin resistance, inflammation and lipotoxicity.
A critical remaining question is “how does as UBSC adipocyte differ from a LBSC adipocyte?”. To answer this question we collected LBSC and UBSC adipose tissue, adipocytes, and pre-adipocytes from healthy, young prototypically ‘normal’ men and women. The women all had a normal gynoid ‘pear’ shaped body fat distribution and the men were android or ‘apple’ shaped. Our hypothesis was that subjecting LBSC and UBSC adipose tissue to deep mRNA, miRNA, and lncRNA profiling would identify novel differences in the transcriptome. Furthermore, if the differences were maintained ex-vivo in pre-adipocytes cultured from these same regions , we hypothesized that that this would support epigenetic programming of these key tissues and reveal a deeper understanding of the mechanism(s) responsible for the protective effects of LBSC adipose tissue.
We will discuss the mRNAs, miRNAs, and lncRNAs that are differentially expressed between LBSC and UBSC, chromosomal hot spots that appear to govern the RNA differences, and new data on the role of epigenetic programming as a mechanism underlying these differences. Several HOX genes (Chr. 12 and 7) appear critical to the cell autonomous program, & we will highlight a lncRNA called HOTAIR that may set the epigenetic program in motion. We will also peer into the future and explore how this information might inform new preventive strategies through the early identification of critical epigenetic programming which determines CV disease risk.