Chronic Pancreatitis Is Characterized by Elevated Circulating Periostin Levels Related to Intra-Pancreatic Fat Deposition

Abstract

Background Periostin is a matricellular protein that induces fibrillogenesis and activates cell migration. It is overexpressed in common fibrotic diseases and is also associated with abdominal adiposity/ectopic fat phenotypes. The study aimed to investigate circulating levels of periostin in health and after an attack of pancreatitis, as well as their associations with abdominal adiposity/ectopic fat phenotypes. Methods Blood samples were obtained from healthy controls, as well as definite chronic pancreatitis (CP) and acute pancreatitis (AP) individuals during follow-up visits. Fat depositions in the pancreas, liver, skeletal muscle, as well as visceral and subcutaneous fat volumes, were quantified with the use of magnetic resonance imaging. A series of multivariable analyses were conducted, accounting for possible confounders. Results A total of 121 individuals were included. Periostin levels were significantly higher in the CP group compared with the other groups in both unadjusted (F = 3.211, P = 0.044) and all adjusted models (F = 4.165, P = 0.019 in the most adjusted model). Intra-pancreatic fat deposition (but not the other fat phenotypes) was significantly associated with periostin concentration in the CP group (β = 49.63, P = 0.034) and explained most of its variance (32.0%). Conclusions Individuals with CP, but not healthy individuals or those after clinical resolution of AP, are characterized by elevated circulating levels of periostin that are positively associated with intra-pancreatic fat deposition.

Intrapancreatic, Liver, and Skeletal Muscle Fat Depositions in First Attack of Acute Pancreatitis Versus Health

“…Specifically, people with high IPFD have a significantly increased risk of developing first attack of acute pancreatitis (which in the context of our research question would essentially be “steatopancreatitis” if one were to draw a parallel with NASH). The existence of this initial link has been suggested in this study for the first time, whereas the existence of subsequent links was shown in previous studies: both end-stage chronic pancreatitis (which in the context of our research question would be analogous to cirrhosis) and pancreatic ductal adenocarcinoma (which in the context of our research question would be analogous to hepatocellular carcinoma) are both known to be characterized by high IPFD (13,15,23,40). As IPFD may increase because of excessive alcohol consumption and coexisting diabetes, we were careful not to consider these in the study groups.…”

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study

“…This resulted in a small number of cases, which may be the reason for the unstable results. For CP, studies have reported the relationship between IPFD and its incidence, but our study did not analyze these individuals separately owing to the small number of participants with CP (10,34). Overall, the above findings provide a strong support for the PANcreatic Diseases Originating from intRa-pancreatic fAt (PANDORA) hypothesis, which postulates that increased IPFD is the single most important driver for diseases of both the exocrine pancreas and the endocrine pancreas (4).…”

Association between Intrapancreatic Fat Deposition and the Leptin/Ghrelin Ratio in the Fasted and Postprandial States

“…Leptin is known to promote the production of type 1 collagen and growth factor β1 by activated stellate cells [24]. Hence, it is possible that leptin contributes to reduced regenerative capacity of the pancreas, fibrosis, and fatty replacement of pancreatic acini via pancreatic stellate cells [25]. Leptin may also affect the endocrine pancreas as β cells are known to express the leptin receptor [26].…”