Pancreatic Fat Accumulation, Fibrosis, and Acinar Cell Injury in the Zucker Diabetic Fatty Rat Fed a Chronic High-Fat Diet

Matsuda, Akiko; Makino, Naohiko; Tozawa, Tomohiro; Shirahata, Nakao; Honda, Takao; Ikeda, Yushi; Sato, Hideyuki; Ito, Miho; Kakizaki, Yasuharu; Akamatsu, Manabu; Ueno, Yoshiyuki; Kawata, Sumio

doi:10.1097/mpa.0000000000000129

Cited by 66 publications

(56 citation statements)

References 51 publications

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“…In the present study, histological examination of pancreatic acinar cells in HFD-induced obese rats revealed marked accumulation of fat droplets, indicating ectopic fat deposition in the pancreas. Similar results were found in animal models of metabolic syndrome [24,25]. In parallel, HFD-fed rats also showed a marked increase in TG levels in the pancreas along with up-regulated SREBP-1c expression.…”

Section: Discussionsupporting

confidence: 73%

Rice bran water extract attenuates pancreatic abnormalities in high-fat diet-induced obese rats

Parklak¹,

Munkong²,

Somnuk³

et al. 2017

Trop. J. Pharm Res

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Section: Discussionsupporting

confidence: 73%

Rice bran water extract attenuates pancreatic abnormalities in high-fat diet-induced obese rats

Parklak¹,

Munkong²,

Somnuk³

et al. 2017

Trop. J. Pharm Res

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“…We recently demonstrated that intra-lobular fat accumulates in exocrine pancreatic tissue and that lipid droplets in acinar cells increase in Zucker diabetic fatty rats, which is an animal model of type 2 diabetes caused by the chronic intake of a high-fat diet. These conditions appear cause acinar cell injury and fibrosis[21]. Thus, additional clinical and experimental studies of the interrelationships between diabetes, metabolic syndrome and pancreatic injury should be conducted to clarify the pathogenesis of “non-alcoholic fatty pancreatic disease”.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic hyperechogenicity associated with hypoadiponectinemia and insulin resistance: A Japanese population study

Makino

Shirahata

Honda

et al. 2016

WJH

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AIMTo examine the relationship between pancreatic hyperechogenicity and risk factors for metabolic syndrome.METHODSA general population-based survey of lifestyle-related diseases was conducted from 2005 to 2006 in Japan. The study involved 551 participants older than 40 year of age. Data for 472 non-diabetic adults were included in the analysis. The measures included the demographic factors, blood parameters, results of a 75 g oral glucose tolerance test, and abdominal ultrasonography. The echogenicity of the pancreas and liver was compared, and then the subjects were separated into two groups: cases with pancreatic hyperechogenicity (n = 208) and cases without (controls, n = 264). The differences between both groups were compared using an unpaired t-test or Fisher’s exact test. Multiple logistic regression analysis was used to determine the relationship between the pancreatic hyperechogenicity and clinical and biochemical parameters.RESULTSSubjects with pancreatic hyperechogenicity had decreased serum adiponectin concentration compared to control subjects [8.9 (6.5, 12.8) vs 11.1 (7.8, 15.9), P < 0.001] and more frequently exhibited features of metabolic syndrome. Logistic regression analysis showed that the following variables were significantly and independently associated with pancreatic hyperechogenicity: Presence of hypoadiponectinemia, increased body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) score, and presence of fatty liver. Similar associations were also observed in subjects with pancreatic hyperechogenicity without fatty liver. Multivariate association analysis of data from participants without fatty liver showed that hypoadiponectinemia was significantly associated with pancreatic hyperechogenicity (OR = 0.93, 95%CI: 0.90 - 0.97, P < 0.001). This association was independent of other confounding variables. Additionally, an increased BMI and higher HOMA-IR score were significantly associated with pancreatic hyperechogenicity.CONCLUSIONPancreatic hyperechogenicity is independently associated with increased BMI, insulin resistance, and hypoadiponectinemia in the general population.

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“…In particular, adipocytes in WAT abundantly express the angiotensin II type-1 receptor (AT1) (23, 24), a major pro-fibrotic pathway that becomes activated in a pro-inflammatory environment (23, 24). Obesity also leads to fat accumulation in the normal pancreas (steatosis), which generates a similar inflammatory process within the pancreas itself, with increased expression of cytokines, extracellular matrix remodeling, and fibrosis (7, 25, 26). Importantly, cancer lesions in obese mice and patients have an increased adipocyte content (27, 28).…”

Section: Introductionmentioning

confidence: 99%

Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy

et al. 2016

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It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacological inhibition of angiotensin-II type-1 receptor (AT1) reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSCs) in obesity is induced by tumor-associated neutrophils (TANs) recruited by adipocyte-secreted IL-1β. PSCs further secrete IL-1β, and inactivation of PSCs reduces IL-1β expression and TAN recruitment. Furthermore, depletion of TANs, IL-1β inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In pancreatic cancer patients, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that crosstalk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity.

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Pancreatic Fat Accumulation, Fibrosis, and Acinar Cell Injury in the Zucker Diabetic Fatty Rat Fed a Chronic High-Fat Diet

Abstract: Supplemental digital content is available in the text.

Cited by 66 publications

References 51 publications

Rice bran water extract attenuates pancreatic abnormalities in high-fat diet-induced obese rats

Rice bran water extract attenuates pancreatic abnormalities in high-fat diet-induced obese rats

Pancreatic hyperechogenicity associated with hypoadiponectinemia and insulin resistance: A Japanese population study

Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy

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