Abstract
Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional. Insulin concentrations and release are fat mass- and LDs-dependent respectively. Fat reduction mediated by bariatric surgery repairs obesity-associated T2D. The expression of genes, like PCSK1 (proinsulin conversion enzyme), GCG (Glucagon), GPLD1, CD38 and NNAT, involved in insulin regulation/release were differentially expressed in pancreas and adipose tissue (AT). INS (insulin) and GCG expression reduced in human AT-T2D as compared to AT-control, but remained unchanged in pancreas in either state. Insulin levels (mRNA/protein) were higher in AT derived from prediabetes BB rats with destructed pancreatic β-cells and controls than pancreas derived from the same rats respectively. Insulin expression in 10 human primary cell types including adipocytes and macrophages is an evidence for extrapancreatic insulin-producing cells. The data suggest a crosstalk between AT and pancreas to fine-tune energy metabolic system or may minimize the metabolic damage during diabetes. This study opens new avenues towards T2D therapy with a great impact on public health.
Highlights
Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as type 2 diabetes (T2D)
To confirm our microscopy approach to assess adipocyte-fraction purity, the expression of five known mRNA markers for human adipocytes and one for preadipocytes were measured. mRNA expression displayed a significant up-regulation of the five mRNA markers in both visceral and subcutaneous adipocytes, i.e. DGAT2, LEP, LIPE, LPL and FSP27 (Figure 1 C–D) as compared to human preadipocytes, and AEBP-1 was significantly up-regulated in both human preadipocytes as compared to human adipocytes (Figure 1 E)
The mRNA expression data convincingly showed the expression of INS gene in all 16 measurements
Summary
Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. The role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Hypertrophy of adipocytes is the main cause of obesity[7,8,9] These results from the excessive storage of energy in the form of triglycerides (TGs) in lipid droplets (a monolayer www.nature.com/scientificreports membrane with a structure similar to very low-density lipoprotein10) within adipocytes, which links to obesity and to IR. In spite of increasing studies on the properties of AT and in particular adipocytes, the mechanisms that lead to obesity-induced pathophysiological states are still poorly understood. We chose to study human primary adipocytes alone to avoid AT complexity and obtain a clear detailed picture of human adipocytes and its link with obesity and insulin regulation
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