Pancreatic Adipose Tissue in Diet-Induced Type 2 Diabetes

Abstract

Obesity represents one of the most important health problems. Proper adipose tissue expandability is crucial for avoiding metabolic disorders. Furthermore, not all fat depots are functionally equal. Our previous work indicates that the expansion of the mesenteric adipose tissue (MWAT) plays a role in the intestinal barrier. Whether pancreas-associated adipose tissue (PAT) has a specific function is currently unknown. We hypothesize that storage of excess nutrients in PAT and PAT-derived adipokines (such as adiponectin) protect the pancreas against metabolic dysfunction during weight gain/obesity. An initial morphological study showed that PAT has an increased number of small, but fewer large adipocytes relative the adjacent MWAT. We compared the response to a 16-week high-fat diet (HFD)/obesity between PAT, other fat depots and pancreas. We found higher mRNA expression of inflammation markers in MWAT, inguinal (IWAT) and gonadal fat (GWAT), but not in PAT in response to HFD/obesity. HFD also downregulated the expression of insulin receptor and adiponectin in all fat depots, but not in PAT. The pancreas showed an increase in inflammatory and insulin resistance markers only after long-term (16 weeks) HFD exposure, a time point when also PAT displayed a reduction in insulin receptor and adiponectin expression. Smaller adipocytes are typically more functional than large adipocytes. Thus, these data suggest that PAT have an increased capacity for energy storage. This in turn may protect the pancreas against ectopic lipid accumulation and lipotoxicity. Moreover, our data show that PAT is protected against the deleterious effects of HFD, maintaining normal mRNA levels of adiponectin, insulin receptor and markers of inflammation. In summary, we believe that PAT protects the pancreatic beta-cells from lipotoxicity through its increased capacity for energy storage, sustained insulin sensitivity and possibly also increased insulin exposure because of its anatomical location. Disclosure B. Chanclon Garcia: None. Y. Wu: None. E. Banke Nordbeck: None. S. Musovic: None. C.S. Olofsson: None. P. Rorsman: None. I. Wernstedt Asterholm: None.