Circulating levels of lipocalin-2 are associated with fatty pancreas but not fatty liver

Singh, Ruma G.; Nguyen, Ngoc Nhu; Cervantes, Aya; Kim, Jin U.; Stuart, Charlotte E; Petrov, Maxim S.

doi:10.1016/j.peptides.2019.170117

Cited by 21 publications

(12 citation statements)

References 46 publications

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“…Single-voxel spectroscopy was used and the voxel (20 × 20 × 20 mm) was positioned in the right lobe of the liver (away from the blood vessels and bile ducts and ≥ 1 cm away from the edge) [ 22 ]. Fifty acquisitions were recorded in a measuring time of 5 min, and automated abdominal shimming was performed with TR = 3,000 ms and TE = 33 ms.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…Humans express LCN2 in multiple tissues, such as adipose [18], lymphatic (bone marrow and spleen) [20,21], respiratory (bronchus, nasopharynx), digestive (stomach and salivary gland) [22], genitourinary (cervix and uterus), endocrine [23], muscle [24], and other immune cells in addition to the previously identified neutrophils [25]. Several studies have revealed that neoplastic tissues originating from the pancreas, colon, breast, and lung express elevated LCN2 levels when compared to normal tissues [25].…”

Section: Introductionmentioning

confidence: 99%

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Santiago-Sánchez

Pita-Grisanti

Quiñones-Díaz

et al. 2020

IJMS

105

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Lipocalin-2 (LCN2) is a secreted glycoprotein linked to several physiological roles, including transporting hydrophobic ligands across cell membranes, modulating immune responses, maintaining iron homeostasis, and promoting epithelial cell differentiation. Although LNC2 is expressed at low levels in most human tissues, it is abundant in aggressive subtypes of cancer, including breast, pancreas, thyroid, ovarian, colon, and bile duct cancers. High levels of LCN2 have been associated with increased cell proliferation, angiogenesis, cell invasion, and metastasis. Moreover, LCN2 modulates the degradation, allosteric events, and enzymatic activity of matrix metalloprotease-9, a metalloprotease that promotes tumor cell invasion and metastasis. Hence, LCN2 has emerged as a potential therapeutic target against many cancer types. This review summarizes the most relevant findings regarding the expression, biological roles, and regulation of LCN2, as well as the proteins LCN2 interacts with in cancer. We also discuss the approaches to targeting LCN2 for cancer treatment that are currently under investigation, including the use of interference RNAs, antibodies, and gene editing.

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“…It is hypothesized that the former is present in both T2D and PPDM, whereas the latter is present in PPDM only (14). However, although recent studies have provided valuable insights into the mechanisms of IPFD following pancreatitis (27)(28)(29)(30)(31), no purposely designed study has investigated the difference in IPFD between PPDM and T2D. Future investigations should clarify the intricate relationship between PPDM, IPFD, and pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Postpancreatitis Diabetes Confers Higher Risk for Pancreatic Cancer Than Type 2 Diabetes: Results From a Nationwide Cancer Registry

2020

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Pancreatitis and diabetes are established risk factors for pancreatic cancer. However, to date, studies have investigated only the risk associated with either of them alone. The aim of this study was to investigate the effect of pancreatitis and diabetes combined, as well as their temporal relationship, on the risk of pancreatic cancer. RESEARCH DESIGN AND METHODSNationwide cancer registry was linked to hospital discharge and mortality data from 1998 to 2015 in New Zealand. Incidence of primary pancreatic cancer in the four study groups (type 2 diabetes [T2D] alone, pancreatitis alone, T2D followed by pancreatitis, and postpancreatitis diabetes mellitus [PPDM]) was identified. Multivariable Cox regression analyses were conducted, with T2D as the reference group. A head-to-head comparison between the T2D followed by pancreatitis and PPDM groups was also performed. RESULTSAmong 139,843 individuals (735,541 person-years), 913 (0.7%) were diagnosed with pancreatic cancer. The proportion of pancreatic cancer was 3.1%, 2.3%, 2.0%, and 0.6% in individuals with PPDM, T2D followed by pancreatitis, pancreatitis alone, and T2D alone, respectively. PPDM (hazard ratio [HR] 6.94; 95% CI 4.09-11.77) and T2D followed by pancreatitis (HR 5.35; 95% CI 3.52-8.14) were associated with significantly higher risks of pancreatic cancer compared with T2D alone. In the headto-head comparison, PPDM was associated with a higher risk of pancreatic cancer compared with T2D followed by pancreatitis (HR 2.35; 95% CI 1.12-4.93). CONCLUSIONSPancreatitis significantly increases the risk of pancreatic cancer in individuals with diabetes. In particular, PPDM poses the highest risk for pancreatic cancer.Pancreatic cancer is one of the leading causes of cancer-specific mortality, with a 5-year survival rate of ,10% (1), and it is projected to become the leading cause of cancer deaths by 2050 (2). Diabetes is often regarded as a risk factor for pancreatic cancer. A meta-analysis of 35 cohort studies reported that individuals with diabetes were at a 1.9-times-higher risk for pancreatic cancer compared with the risk for those

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Circulating levels of lipocalin-2 are associated with fatty pancreas but not fatty liver

Cited by 21 publications

References 46 publications

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

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

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Postpancreatitis Diabetes Confers Higher Risk for Pancreatic Cancer Than Type 2 Diabetes: Results From a Nationwide Cancer Registry

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