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Ko J, Petrov MS. Intra-Pancreatic Fat Deposition and Pancreatitis: Insights from the COSMOS Program. Diabetes Metab Syndr Obes 2025; 18:1489-1500. [PMID: 40356715 PMCID: PMC12067683 DOI: 10.2147/dmso.s400276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 04/30/2025] [Indexed: 05/15/2025] Open
Abstract
The global burden of pancreatitis is substantial, bedevilled by the lack of pathogenesis-based treatments for acute pancreatitis and chronic pancreatitis. The integrated PANDORA (PANcreatic Diseases Originating from intRa-pancreatic fAt) hypothesis "moved the needle" on thinking why pancreatitis develops by bringing fat in the pancreas to the fore. A total of 20 original clinical studies exploring an uncharted territory of fat in the pancreas and pancreatitis were published between 2019 and 2024 as part of the COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS) program. This review concisely summarises the novel insights into the relationship of intra-pancreatic fat deposition with endocrine and exocrine pancreatic functions, behavioural and nutritional factors, as well as various biomarkers. Tapping into the wealth of knowledge derived from the COSMOS program can unlock new perspectives on the treatment of acute pancreatitis and chronic pancreatitis.
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Affiliation(s)
- Juyeon Ko
- College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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Ye J, Wang JG, Liu RQ, Shi Q, Wang WX. Association between intra-pancreatic fat deposition and diseases of the exocrine pancreas: A narrative review. World J Gastroenterol 2025; 31:101180. [PMID: 39811515 PMCID: PMC11684206 DOI: 10.3748/wjg.v31.i2.101180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/26/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
Intrapancreatic fat deposition (IPFD) has garnered increasing attention in recent years. The prevalence of IPFD is relatively high and associated with factors such as obesity, age, and sex. However, the pathophysiological mechanisms underlying IPFD remain unclear, with several potential contributing factors, including oxidative stress, alterations in the gut microbiota, and hormonal imbalances. IPFD was found to be highly correlated with the occurrence and prognosis of exocrine pancreatic diseases. Although imaging techniques remain the primary diagnostic approach for IPFD, an expanding array of biomarkers and clinical scoring systems have been identified for screening purposes. Currently, effective treatments for IPFD are not available; however, existing medications, such as glucagon-like peptide-1 receptor agonists, and new therapeutic approaches explored in animal models have shown considerable potential for managing this disease. This paper reviews the pathogenesis of IPFD, its association with exocrine pancreatic diseases, and recent advancements in its diagnosis and treatment, emphasizing the significant clinical relevance of IPFD.
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Affiliation(s)
- Jing Ye
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Jian-Guo Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Rong-Qiang Liu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Qiao Shi
- Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Wei-Xing Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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3
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Petrov MS. Pancreatitis as a Matter of Fat: The Causal Role of High Intrapancreatic Fat Deposition. Am J Gastroenterol 2024:00000434-990000000-01359. [PMID: 39364877 DOI: 10.14309/ajg.0000000000003065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Accepted: 08/08/2024] [Indexed: 10/05/2024]
Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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Habas E, Farfar K, Habas E, Rayani A, Elzouki AN. Extended Review and Updates of Nonalcoholic Fatty Pancreas Disease. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2024; 12:284-291. [PMID: 39539795 PMCID: PMC11556510 DOI: 10.4103/sjmms.sjmms_526_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 11/16/2024]
Abstract
Non-alcoholic fatty pancreatic disease (NAFPD), also known as pancreatic steatosis, is a benign condition characterized by deposition of lipids in the pancreas and is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, aging, and absence of heavy alcohol intake or infection. Similar to nonalcoholic fatty liver disease, NAFPD is a phenotypic entity that includes fat buildup in the pancreas, pancreatic inflammation, and subsequent fibrosis. The extent to which pancreatic fat infiltration is clinically important remains unclear. Despite these clinical associations, most of the clinical effects of NAFPD are not known. NAFPD may be identified by transabdominal and elastography ultrasound, computed tomography scan, or magnetic resonance imaging modalities, but a confirmatory diagnosis can only be made through tissue histology. In addition to complications such as acute and chronic pancreatitis, NAFPD may progress to pancreatic ductal adenocarcinoma. However, further research is required to fully understand the associations, pathophysiology, and effects of NAFPD. This review provides a narrative synthesis of the current literature on the epidemiology, pathophysiology, complications, diagnostic and imaging tools, and management of NAFPD.
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Affiliation(s)
- Elmukhtar Habas
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
| | - Kalifa Farfar
- Department of Medicine, Alwakra General Hospital, Alwakra, Qatar
| | - Eshrak Habas
- Department of Medicine, Tripoli Central Hospital, Tripoli, Libya
| | - Amnna Rayani
- Tripoli Children Hospital, Medical College, Tripoli University, Tripoli, Libya
| | - Abdul-Naser Elzouki
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
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Dong X, Zhu Q, Yuan C, Wang Y, Ma X, Shi X, Chen W, Dong Z, Chen L, Shen Q, Xu H, Ding Y, Gong W, Xiao W, Wang S, Li W, Lu G. Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study. Am J Gastroenterol 2024; 119:1158-1166. [PMID: 38587286 PMCID: PMC11142652 DOI: 10.14309/ajg.0000000000002792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 03/19/2024] [Indexed: 04/09/2024]
Abstract
INTRODUCTION To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. METHODS A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content. RESULTS Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179-1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058-1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132-1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192-7.234), pancreatic cancer (HR 1.976, 95% CI 1.054-3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122-1.593, P = 0.001). DISCUSSION FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas.
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Affiliation(s)
- Xiaowu Dong
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Qingtian Zhu
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Chenchen Yuan
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Yaodong Wang
- Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Suzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine of Digestive Diseases, Kunshan Affiliated Hospital of Yangzhou University, Kunshan, China
| | - Xiaojie Ma
- Department of Critical Care Medicine, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xiaolei Shi
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Weiwei Chen
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Zhao Dong
- Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Lin Chen
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Qinhao Shen
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Hongwei Xu
- Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Suzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine of Digestive Diseases, Kunshan Affiliated Hospital of Yangzhou University, Kunshan, China
| | - Yanbing Ding
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Weijuan Gong
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Weiming Xiao
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Shengfeng Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Weiqin Li
- Department of Critical Care Medicine, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guotao Lu
- Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
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Xiao Y, Han L, Wang H, Ke H, Xu S, Huang Z, Lyu G, Li S. Uric Acid Inhibits Mice Pancreatic Steatosis via the Glycerophospholipid Pathway. ACS OMEGA 2024; 9:21829-21837. [PMID: 38799326 PMCID: PMC11112710 DOI: 10.1021/acsomega.3c08874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 04/26/2024] [Accepted: 04/30/2024] [Indexed: 05/29/2024]
Abstract
Background: despite evidence for mutually reinforcing effects of serum uric acid (SUA) and lipids, the effects of uric levels on pancreatic steatosis are not well-established. In this study, the relationship between low concentrations of uric acid and pancreatic steatosis was evaluated. Methods: forty C57BL/6J mice were fed a diet of high uric acid (HU), high fat (HF), high uric acid and high fat (HUHF), and normal control (NC) (10 mice in each group). Weight was measured weekly. Ultrasonography was performed to observe the pancreatic echo intensity of all mice before the end of feeding. Subsequently, peripheral blood was taken for biochemical examination. Intact pancreatic tissues were taken, part of which was used for pathological examination, part of which was used for PCR experiments and Western Blot experiments to obtain glycerophospholipid-associated mRNA data and protein levels. Results: body weight was significantly higher in the HF group than in the other three groups. Higher uric acid matched lower total cholesterol and triglyceride, matched higher low-density lipoprotein, and matched equal high-density lipoprotein. Ultrasound images and HE staining of pancreatic tissues of mice showed that higher uric acid matched lower fat content. The mRNA levels of phospholipase A2 group IB were highest in high uric acid group, while relative protein expression levels were lowest in high uric acid and control groups. Phospholipase A2 group IIA showed the opposite patterns. Conclusions: elevated serum uric acid at low concentrations can inhibit pancreatic steatosis, which is modulated via the glycerophospholipid metabolic pathway.
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Affiliation(s)
- Yang Xiao
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
| | - Lina Han
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
| | - Han Wang
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
| | - Helin Ke
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
| | - Shaodan Xu
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
| | - Zhibin Huang
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
| | - Guorong Lyu
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
- Department
of Medicine, Quanzhou Medical College, Quanzhou 362002, China
| | - Shilin Li
- Department
of Ultrasonography, Second Affiliated Hospital
of Fujian Medical University, Quanzhou 362002, China
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7
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Shamaitijiang X, Kimita W, Ko J, Skudder-Hill L, Liu Y, Petrov MS. Relationship of Liver Blood Tests and T1 Relaxation Time With Intra-pancreatic Fat Deposition. J Clin Exp Hepatol 2024; 14:101343. [PMID: 38304879 PMCID: PMC10827601 DOI: 10.1016/j.jceh.2023.101343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 12/26/2023] [Indexed: 02/03/2024] Open
Abstract
Background Liver is well recognised as a metabolically active organ. While intra-pancreatic fat deposition (IPFD) is emerging as an important player in the whole-body metabolism, the interplay between the liver and IPFD has been poorly investigated. This study aimed to investigate the associations of liver blood tests and non-invasive tests for hepatic fibrosis with IPFD. Methods Participants underwent a 3.0 Tesla magnetic resonance imaging to measure IPFD and map liver T1 (longitudinal relaxation time). Four liver tests were done on the same sample of blood. Hepatic fibrosis risk score (BARD) was calculated. Linear regression models were built, accounting for age, sex, visceral-to-subcutaneous fat ratio, and other covariates. Results A total of 143 individuals were studied. In the most adjusted model, alkaline phosphatase (P < 0.001), alanine aminotransferase (P < 0.001), and γ-glutamyl transferase (P = 0.042) were significantly positively associated with IPFD. The BARD score was not significantly associated with IPFD in the most adjusted model (P = 0.295). T1 relaxation time of the liver was not significantly associated with IPFD in the most adjusted model (P = 0.782). Conclusions Elevated alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transferase are associated with increased IPFD. Hepatic fibrosis does not appear to be associated with IPFD.
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Affiliation(s)
| | - Wandia Kimita
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Juyeon Ko
- School of Medicine, University of Auckland, Auckland, New Zealand
| | | | - Yutong Liu
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Maxim S. Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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Petrov MS. The Pharmacological Landscape for Fatty Change of the Pancreas. Drugs 2024; 84:375-384. [PMID: 38573485 PMCID: PMC11101365 DOI: 10.1007/s40265-024-02022-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/07/2024] [Indexed: 04/05/2024]
Abstract
The quest for medications to reduce intra-pancreatic fat deposition is now quarter a century old. While no specific medication has been approved for the treatment of fatty change of the pancreas, drug repurposing shows promise in reducing the burden of the most common disorder of the pancreas. This leading article outlines the 12 classes of medications that have been investigated to date with a view to reducing intra-pancreatic fat deposition. Information is presented hierarchically-from preclinical studies to retrospective findings in humans to prospective interventional studies to randomised controlled trials. This lays the grounds for shepherding the most propitious drugs into medical practice through well-designed basic science studies and adequately powered randomised controlled trials.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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Petrov MS. Fateful fat: Intra-pancreatic lipids cause pancreatic cancer. Cell Rep Med 2024; 5:101428. [PMID: 38382463 PMCID: PMC10897621 DOI: 10.1016/j.xcrm.2024.101428] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/23/2024]
Abstract
In a Mendelian randomization and prospective cohort study,1 intra-pancreatic fat increases the risk of pancreatic cancer. This provides persuasive human evidence of causal relation between lipids and cancer in the pancreas, which confirms a prediction of the PANDORA hypothesis.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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10
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Chung MJ, Park SW, Lee KJ, Park DH, Koh DH, Lee J, Lee HS, Park JY, Bang S, Min S, Park JH, Kim SJ, Park CH. Clinical impact of pancreatic steatosis measured by CT on the risk of post-ERCP pancreatitis: a multicenter prospective trial. Gastrointest Endosc 2024; 99:214-223.e4. [PMID: 37598866 DOI: 10.1016/j.gie.2023.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 08/09/2023] [Accepted: 08/13/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND AND AIMS Pancreatic steatosis (PS) may be a risk factor for acute pancreatitis. Whether it is also a risk factor for post-ERCP pancreatitis (PEP) has not been evaluated. This study aimed to determine the impact of PS on PEP development. METHODS This multicenter prospective trial enrolled 786 consecutive patients who underwent contrast-enhanced abdominal CT and subsequent first-time ERCP. PS was evaluated based on pancreatic attenuation on unenhanced CT images. The risk of PS for the development of PEP was evaluated using a logistic regression model. RESULTS Of 527 patients included in the study, 157 (29.8%) had PS and 370 (70.2%) did not. At 24 hours after ERCP, there was a significant difference in the PEP identified in 22 patients (14.0%) in the PS group and 23 patients (6.2%) in the "no PS" (NPS) group (P = .017). Diabetes and hypertension were more common in the PS group than in the NPS group; no differences in dyslipidemia were found. Patients with PS had a higher risk for the development of PEP than those with NPS (odds ratio, 2.09; 95% confidence interval, 1.08-4.03). No other variables were identified as risk factors for PEP. CONCLUSIONS PS is a significant risk factor for PEP for which preventive measures should be considered. Standardized measurement protocols to assess PS by CT are needed. (Clinical trial registration number: KCT0006068.).
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Affiliation(s)
- Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Se Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Kyong Joo Lee
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Da Hae Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Dong Hee Koh
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Jin Lee
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seonjeong Min
- Department of Radiology, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Ji Hoon Park
- Division of Gastroenterology, Department of Internal Medicine, CHA Ilsan Medical Center, CHA University, Goyang, Republic of Korea
| | - So Jeong Kim
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
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Kimita W, Skudder-Hill L, Shamaitijiang X, Priya S, Petrov MS. Associations of pancreas fat content and size with markers of iron metabolism. Obes Res Clin Pract 2024; 18:56-63. [PMID: 38278667 DOI: 10.1016/j.orcp.2024.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/28/2024]
Abstract
OBJECTIVE To comprehensively investigate the associations of pancreas fat content and size with circulating markers of iron metabolism. METHODS A total of 116 individuals underwent magnetic resonance imaging and spectroscopy on a 3.0 Tesla scanner, exclusively for the purpose of the COSMOS research programme. Intra-pancreatic fat deposition, total pancreas volume, liver fat content, visceral and subcutaneous fat volumes were quantified. Plasma levels of hepcidin and ferritin were measured. Multiple linear regression analysis was conducted, adjusting for body mass index, age, and sex. RESULTS Total intra-pancreatic fat deposition was inversely associated with hepcidin (β = -0.54, 95 % confidence interval -1.02 to -0.07) whereas total pancreas volume was not associated with hepcidin (β = 0.36, 95 % confidence interval -7.12 to 7.84) in the most adjusted model. Neither total intra-pancreatic fat deposition (β = -0.03, 95 % confidence interval -0.39 to 0.33) nor total pancreas volume (β = -1.02, 95 % confidence interval -6.67 to 4.63) was associated with ferritin in the most adjusted model. Subcutaneous fat, visceral fat, and liver fat were not associated with hepcidin. Subcutaneous fat was inversely associated with ferritin (β = -0.06, 95 % CI -0.11 to -0.01) whereas visceral fat (β = 0.05, 95 % CI -0.01 to 0.14) and liver fat (β = 0.09, 95 % CI -0.04 to 0.34) were not associated with ferritin in the most adjusted model. CONCLUSIONS Increased intra-pancreatic fat deposition, but not other fat depots, is associated with reduced circulating levels of hepcidin. Deranged iron metabolism may play a role in the pathogenesis of fatty change of the pancreas.
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Affiliation(s)
- Wandia Kimita
- School of Medicine, University of Auckland, Auckland, New Zealand
| | | | | | - Sunitha Priya
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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12
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Al-Ani Z, Ko J, Petrov MS. Relationship of Serum Bile Acids with Fat Deposition in the Pancreas, Liver, and Skeletal Muscle. Clin Exp Gastroenterol 2023; 16:137-146. [PMID: 37605644 PMCID: PMC10440115 DOI: 10.2147/ceg.s422995] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 08/10/2023] [Indexed: 08/23/2023] Open
Abstract
Introduction Ectopic fat deposition is well appreciated as a key contributor to digestive and liver diseases. Bile acids have emerged as pleiotropic signalling molecules involved in numerous metabolic pathways. The aim was to study the associations of bile acids with ectopic fat deposition and lipid panel. Methods A single 3.0 Tesla magnetic resonance imaging scanner was employed to measure fat deposition in the pancreas, liver, and skeletal muscle in 76 adults. Blood samples were drawn to determine total bile acids and lipid panel. Linear regression analyses were run, taking into account age, sex, body mass index, and other covariates. Results The studied ectopic fat depots were not significantly associated with levels of total bile acids in serum. Total bile acids were significantly associated high-density lipoprotein cholesterol - consistently in both the unadjusted (p = 0.018) and all adjusted models (p = 0.012 in the most adjusted model). Low-density lipoprotein cholesterol, total cholesterol, and triglycerides were not significantly associated with total bile acids in both the unadjusted and all adjusted models. Conclusion Fat deposition in the pancreas, liver, and skeletal muscle is not associated with circulating levels of total bile acids. High-density lipoprotein cholesterol is the only component of lipid panel that is associated with total bile acids.
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Affiliation(s)
- Zena Al-Ani
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Juyeon Ko
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
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13
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Al-Ani Z, Ko J, Petrov MS. Intra-pancreatic fat deposition across the pancreatitis spectrum and the influence of gut hormones. Dig Liver Dis 2023; 55:1081-1090. [PMID: 36878840 DOI: 10.1016/j.dld.2023.02.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/13/2022] [Accepted: 02/15/2023] [Indexed: 03/08/2023]
Abstract
BACKGROUND AND AIMS Acute pancreatitis (AP) and chronic pancreatitis (CP) often represent parts of the spectrum of disease. While growing evidence indicates that intra-pancreatic fat deposition (IPFD) plays an important role in the pathogenesis of pancreatitis, no study of living individuals has investigated IPFD in both AP and CP. Further, the associations between IPFD and gut hormones remain to be elucidated. The aims were to investigate the associations of IPFD with AP, CP, and health; and to study whether gut hormones affect these associations. METHODS Magnetic resonance imaging on the same 3.0 Tesla scanner was used to determine IPFD in 201 study participants. These participants were arranged into the health, AP, and CP groups. Gut hormones (ghrelin, glucagon-like peptide-1, gastric inhibitory peptide, peptide YY, and oxyntomodulin) were measured in blood, both after an 8-hour overnight fasting and after ingestion of a standardised mixed meal. A series of linear regression analyses was run, accounting for age, sex, ethnicity, body mass index, glycated haemoglobin, and triglycerides. RESULTS Both the AP group and CP group had significantly higher IPFD in comparison with the health group, consistently across all models (p for trend 0.027 in the most adjusted model). Ghrelin in the fasted state had a significant positive association with IPFD in the AP group (but not the CP or health group), consistently across all models (p = 0.019 in the most adjusted model). None of the studied gut hormones in the postprandial state was significantly associated with IPFD. CONCLUSION Fat deposition in the pancreas is similarly high in individuals with AP and those with CP. The gut-brain axis, and more specifically overexpression of ghrelin, may contribute to increased IPFD in individuals with AP.
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Affiliation(s)
- Zena Al-Ani
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Juyeon Ko
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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14
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Lilly AC, Astsaturov I, Golemis EA. Intrapancreatic fat, pancreatitis, and pancreatic cancer. Cell Mol Life Sci 2023; 80:206. [PMID: 37452870 PMCID: PMC10349727 DOI: 10.1007/s00018-023-04855-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 06/29/2023] [Accepted: 07/03/2023] [Indexed: 07/18/2023]
Abstract
Pancreatic cancer is typically detected at an advanced stage, and is refractory to most forms of treatment, contributing to poor survival outcomes. The incidence of pancreatic cancer is gradually increasing, linked to an aging population and increasing rates of obesity and pancreatitis, which are risk factors for this cancer. Sources of risk include adipokine signaling from fat cells throughout the body, elevated levels of intrapancreatic intrapancreatic adipocytes (IPAs), inflammatory signals arising from pancreas-infiltrating immune cells and a fibrotic environment induced by recurring cycles of pancreatic obstruction and acinar cell lysis. Once cancers become established, reorganization of pancreatic tissue typically excludes IPAs from the tumor microenvironment, which instead consists of cancer cells embedded in a specialized microenvironment derived from cancer-associated fibroblasts (CAFs). While cancer cell interactions with CAFs and immune cells have been the topic of much investigation, mechanistic studies of the source and function of IPAs in the pre-cancerous niche are much less developed. Intriguingly, an extensive review of studies addressing the accumulation and activity of IPAs in the pancreas reveals that unexpectedly diverse group of factors cause replacement of acinar tissue with IPAs, particularly in the mouse models that are essential tools for research into pancreatic cancer. Genes implicated in regulation of IPA accumulation include KRAS, MYC, TGF-β, periostin, HNF1, and regulators of ductal ciliation and ER stress, among others. These findings emphasize the importance of studying pancreas-damaging factors in the pre-cancerous environment, and have significant implications for the interpretation of data from mouse models for pancreatic cancer.
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Affiliation(s)
- Anna C Lilly
- Program in Cancer Signaling and Microenvironment, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA, 19111, USA
- Molecular & Cell Biology & Genetics (MCBG) Program, Drexel University College of Medicine, Philadelphia, PA, 19102, USA
| | - Igor Astsaturov
- Program in Cancer Signaling and Microenvironment, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA, 19111, USA
- The Marvin & Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA
| | - Erica A Golemis
- Program in Cancer Signaling and Microenvironment, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA, 19111, USA.
- Department of Cancer and Cellular Biology, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
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15
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Petrov MS. Fatty change of the pancreas: the Pandora's box of pancreatology. Lancet Gastroenterol Hepatol 2023; 8:671-682. [PMID: 37094599 DOI: 10.1016/s2468-1253(23)00064-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 04/26/2023]
Abstract
Prevention of common diseases of the pancreas or interception of their progression is as attractive in theory as it is elusive in practice. The fundamental challenge has been an incomplete understanding of targets coupled with a multitude of intertwined factors that are associated with the development of pancreatic diseases. Evidence over the past decade has shown unique morphological features, distinctive biomarkers, and complex relationships of intrapancreatic fat deposition. Fatty change of the pancreas has also been shown to affect at least 16% of the global population. This knowledge has solidified the pivotal role of fatty change of the pancreas in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. The pancreatic diseases originating from intrapancreatic fat (PANDORA) hypothesis advanced in this Personal View cuts across traditional disciplinary boundaries with a view to tackling these diseases. New holistic understanding of pancreatic diseases is well positioned to propel pancreatology through lasting research breakthroughs and clinical advances.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
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16
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Möller K, Jenssen C, Braden B, Hocke M, Hollerbach S, Ignee A, Faiss S, Iglesias-Garcia J, Sun S, Dong Y, Carrara S, Dietrich CF. Pancreatic changes with lifestyle and age: What is normal and what is concerning? Endosc Ultrasound 2023; 12:213-227. [PMID: 37148135 PMCID: PMC10237602 DOI: 10.4103/eus-d-22-00162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 01/03/2023] [Indexed: 05/07/2023] Open
Abstract
During the aging process, typical morphological changes occur in the pancreas, which leads to a specific "patchy lobular fibrosis in the elderly." The aging process in the pancreas is associated with changes in volume, dimensions, contour, and increasing intrapancreatic fat deposition. Typical changes are seen in ultrasonography, computed tomography, endosonography, and magnetic resonance imaging. Typical age-related changes must be distinguished from lifestyle-related changes. Obesity, high body mass index, and metabolic syndrome also lead to fatty infiltration of the pancreas. In the present article, age-related changes in morphology and imaging are discussed. Particular attention is given to the sonographic verification of fatty infiltration of the pancreas. Ultrasonography is a widely used screening examination method. It is important to acknowledge the features of the normal aging processes and not to interpret them as pathological findings. Reference is made to the uneven fatty infiltration of the pancreas. The differential diagnostic and the differentiation from other processes and diseases leading to fatty infiltration of the pancreas are discussed.
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Affiliation(s)
- Kathleen Möller
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Maerkisch-Oderland, D-15344 Strausberg, Germany
- Brandenburg Institute of Clinical Medicine at Medical University Brandenburg, Neuruppin, Germany
| | - Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Michael Hocke
- Medical Department II, Helios Klinikum Meiningen, Meiningen, Germany
| | - Stephan Hollerbach
- Department of Medicine and Gastroenterology, Allgemeines Krankenhaus, Celle, Germany
| | - André Ignee
- Department of Medical Gastroenterology, Julius-Spital Würzburg, Germany
| | - Siegbert Faiss
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Siyu Sun
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Liaoning Province, China
| | - Yi Dong
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Siliva Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
| | - Christoph F. Dietrich
- Department of Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
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