Obesity as A Risk Factor for Hypertension

Obesity has been a global phenomenon around the globe, leading to a variety of disorders such as metabolic diseases, asthma, and cardiovascular disease. Obesity and overweight are often related to increased levels of aldosterone in the blood, which implies a direct relationship between obesity, high blood pressure and mineralocorticoid levels. Adipocyte is believed to have a part in the fight against homeostasis, and recent studies have now shown that human fat is a highly active endocrine tissue. The research thus examined whether adipocyte secretional products stimulate adrenocortical aldosterone secretion specifically. The steroid genesis in human adrenocortical cells, NCI-H295R and bovine adrenocortical cells, was increased by isolation of human adi-cyte secretion products, focusing on the secretion of mineral corticoids. Finally, hypertension linked to obesity has the direct connection between the metabolism of fat tissue and the production of adrenal mineralocorticoids.


Introduction
Obesity, especially visceral obesity, is closely linked to hypertension of the arteries. This association has been well established in a variety of racial, religious, and socioeconomic populations, and it is not limited to White adipose tissue has long been thought of solely as a source of lipids and, as a result, as a source of energy.
The function of adipose tissue as a highly active endocrine organ and its role in the body's metabolism and homeostasis has only recently been discovered (11). By directly influencing adrenocortical activity, we tested the hypothesis that human adipocyte secretory products are responsible for obesity-related malfunctions in adrenal steroid, especially increased adrenal mineralocorticoid secretion.

Human Tissues
Stable (20-to 35-year-old) women undergoing surgical mammary reduction (n = 10) provided tissue specimens of human adipose tissue. Collagenase digestion was used to separate adipocytes, as mentioned previously (12,13). Under serum-free conditions, isolated floating adipocytes were cultured in DMEM/F12 containing 15 mmol/l HEPES and 2.5 mmol/l L-glutamine, supplemented with 1.125 g/l NaHCO3, 100 U/ml penicillin, and 100 mg/ml streptomycin. Cells were cultured for 24 hours at 37°C in a humidified atmosphere of 5% CO2. The conditioned medium was then carefully collected, preventing the lipid floating on top, and stored at -20°C until needed.

Adrenocortical Cells
Bovine adrenals were obtained from a local slaughterhouse in Nangarhar, Afghanistan and adrenocortical cells were isolated using trypsin digestion and cultured in DMEM/F12 for 3-4 days until 70% confluency was reached (14). DMEM/F12 was used to grow NCI-H295R adrenocortical cells (ATCC) (12).

Results and discussion
Human adipocytes secrete powerful mineralocorticoid-releasing factors, according to our findings. In human NCI-H295R cells, fat cell-derived secretagogues mediated adrenocortical steroidogenesis, with the most prominent effect on aldosterone release (Fig. 1).   Angiotensinogen and angiotensin II are produced in large quantities in adipose tissue. The stimulatory activity of fat cell conditioned medium (FCCM) also in the presence of the angiotensin type 1 receptor antagonist, valsartan, showed that the observed effect was independent of adipose angiotensin II. Adipokinins such as leptin, adiponectin, interleukin-6, and tumor necrosis factor-a may also be ruled out (12). The stimulatory effect was equivalent to that of maximal forskolin stimulation (2 10-5 M, Fig. 1). The action was heat sensitive, could be precipitated with ammonium sulfate, and could be digested by protease, suggesting that protein was involved. Furthermore, adipocytes secrete at least two factors that work together to stimulate aldosterone secretion (12). These findings point to a previously unknown direct role for adipose tissue in adrenocortical function, especially mineralocorticoid secretion.
How do secretory compounds from adipocytes get to the adrenal cortex? Many adipocyte secretory products have an auto/paracrine effect on adipocyte metabolism.
Several causes, though, are emitted into the bloodstream and can be analyzed in plasma (11,15). Mineralocorticoid release factors secreted into the bloodstream from subcutaneous or visceral fat enter the adrenal and induce adrenocortical steroidogenesis in an endocrine fashion. Furthermore, fat cells in the adrenal are often found in close contact with the steroid-producing cells. Direct paracrine associations and potential steroidogenesis stimulation by adipocyte secretory products are made possible by this near cellular proximity.
Our group recently published a case of an intraadrenal myelolipoma associated with ACTH-independent Cushing's syndrome (16), which included heavily intermingled myelolipomatous and adrenocortical tumor cells with plenty of clear cell-cell interaction (Fig. 3). It's possible that the increased cortisol secretion in this patient was due to paracrine effects of secretory products from myelolipoma cells.
As a result, we suggest that mineralocorticotropic factors derived from adipocytes can promote aldosterone synthesis and secretion in an endocrine or paracrine manner, resulting in hyperaldosteronism and, as a result, hypertension in obesity. This points to a clear relation between fat cell mass and blood pressure. The discovery and further characterization of these causes could lead to new therapeutic options for obesity-related hypertension.