A Systematic Review of Intra-pancreatic Fat Deposition and Pancreatic Carcinogenesis

Sreedhar, Uma L. S.; DeSouza, Steve V.; Park, Brittany; Petrov, Maxim S.

doi:10.1007/s11605-019-04417-4

Cited by 50 publications

(53 citation statements)

References 55 publications

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“…However, given that the present study focused on non-obese individuals only, a pancreas-centered mechanism is likely to explain increased insulin resistance in individuals with NODAP. The possible pancreas-centered mechanism is fatty replacement of the pancreas triggered by recurrent insults to the organ [50]. Recurrent or low-grade persistent inflammation of the pancreas may facilitate fatty replacement in the damaged pancreatic acinar cells via acinar-to-adipocyte transdifferentiation, subsequently leading to IPFD [51].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

Skudder-Hill

Cho

et al. 2020

Nutrients

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Both type 2 prediabetes/diabetes (T2DM) and new-onset prediabetes/diabetes after acute pancreatitis (NODAP) are characterized by impaired tissue sensitivity to insulin action. Although the outcomes of NODAP and T2DM are different, it is unknown whether drivers of insulin resistance are different in the two types of diabetes. This study aimed to investigate the associations between abdominal fat phenotypes and indices of insulin sensitivity in non-obese individuals with NODAP, T2DM, and healthy controls. Indices of insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA-IS), Raynaud index, triglyceride and glucose (TyG) index, Matsuda index) were calculated in fasting and postprandial states. Fat phenotypes (intra-pancreatic fat, intra-hepatic fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using magnetic resonance imaging and spectroscopy. Linear regression and relative importance analyses were conducted. Age, sex, and glycated hemoglobin A1c were adjusted for. A total of 78 non-obese individuals (26 NODAP, 20 T2DM, and 32 healthy controls) were included. Intra-pancreatic fat was significantly associated with all the indices of insulin sensitivity in the NODAP group, consistently in both the unadjusted and adjusted models. Intra-pancreatic fat was not significantly associated with any index of insulin sensitivity in the T2DM and healthy controls groups. The variance in HOMA-IS was explained the most by intra-pancreatic fat (R2 = 29%) in the NODAP group and by visceral fat (R2 = 21%) in the T2DM group. The variance in the Raynaud index was explained the most by intra-pancreatic fat (R2 = 18%) in the NODAP group and by visceral fat (R2 = 15%) in the T2DM group. The variance in the TyG index was explained the most by visceral fat in both the NODAP group (R2 = 49%) and in the T2DM group (R2 = 25%). The variance in the Matsuda index was explained the most by intra-pancreatic fat (R2 = 48%) in the NODAP group and by visceral fat (R2 = 38%) in the T2DM group. The differing association between intra-pancreatic fat and insulin resistance can be used to differentiate NODAP from T2DM. Insulin resistance in NODAP appears to be predominantly driven by increased intra-pancreatic fat deposition.

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Section: Discussionmentioning

confidence: 99%

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

Skudder-Hill

Cho

et al. 2020

Nutrients

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“…Although the pathophysiology of IPFD in individuals with pancreatitis has been poorly investigated, it is likely that adipocytes in the pancreas affect the functions of acinar and islet cells [ 36 , 37 ]. One possible mechanism of IPFD in individuals with CP is related to changes in cellular identity within the pancreas [ 38 , 39 ]. A 2019 clinical study investigating the possible involvement of inflammation in pancreatic β-cell dedifferentiation in individuals with CP (independent of diabetes mellitus) showed that 10% of β-cells lose their identity and mature/differentiated phenotype and regress to a precursor-like dedifferentiated state due to chronic inflammation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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

Stuart

Modesto

et al. 2020

J Clin Med Res

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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.

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“…Although the existence of intrapancreatic fat has been known for several decades [127], our understanding of its origin and functional importance is very limited. Several studies have reported an increased fat deposition in the pancreas in human and murine obesity [127][128][129][130], and intrapancreatic fat has been suggested to contribute to the pathogenesis and severity of acute/chronic pancreatitis, T2DM, and PDAC [131][132][133][134]. Using computer tomography analyses the intrapancreatic fat volume was 32 and 68% greater in the overweight and obese groups, respectively, compared with lean subjects [130].…”

Section: Intrapancreatic Adipose Tissuementioning

confidence: 96%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

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A Systematic Review of Intra-pancreatic Fat Deposition and Pancreatic Carcinogenesis

Cited by 50 publications

References 55 publications

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

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

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

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