Intra-pancreatic Fat Deposition Research Articles

Hyperplasia of fat-containing cells with mature adipocyte marker is associated with pancreatic fat enlargement

Abstract Objectives: The purpose was to elucidate the specific characteristics of fat-containing cells in the pancreas and the mechanism of intra-pancreatic fat deposition (IPFD) in humans. Methods: 15 Japanese patients who had undergone pancreatic resection were enrolled and the normal region of pancreatic samples from each patient was examined. To evaluate the characteristics of fat-containing cells, immunostaining for adiponectin and perilipin 1 was performed and the relationships between the pancreatic fat-cell area or clinical parameters, and the density or the diameter of the fat cells was analyzed. Results: Expression of adiponectin in the cytoplasm and perilipin 1 along the plasma membrane were observed in fat-containing cells in the pancreas. The fat-containing cell area had a significant positive correlation with cell density (r = 0.58, p = 0.023). In addition, fat-containing cell density was significantly positively correlated with homeostasis model assessment insulin resistance (HOMA-IR) (r = 0.61, p = 0.045). Fat-containing cell area was not significantly correlated with cell diameter (r = 0.45, p = 0.095). The diameter of fat-containing cells had significant positive correlations with BMI (r = 0.79, p < 0.001), fasting immunoreactive insulin (r = 0.65, p = 0.029) and HOMA-IR (r = 0.80, p = 0.003). Of all fat-containing cells, 10.4% were intralobular cells, and the diameter of intralobular cells showed a tendency for positive correlation with age (r = 0.52, p = 0.057). Conclusions: The characteristics of fat-containing cells in the pancreas indicate that some of them may be mature adipocytes, and fat volume may be increased by hyperplasia of fat-containing cells associated with insulin resistance. Key terms: pancreatic fat, adipocytes markers, hyperplasia of fat-containing cells, insulin resistance.

The moderating effect of cardiometabolic factors on the association between hepatic and intrapancreatic fat.

Previous studies have investigated the association between hepatic fat and intrapancreatic fat deposition (IPFD); however, results have been inconclusive. The presence of cardiometabolic factors in certain subpopulations could explain this discrepancy. The aim of the present study was to use moderation analyses to determine the conditions under which hepatic fat is associated with IPFD. All participants underwent 3T abdominal magnetic resonance imaging (MRI) and spectroscopy. Hepatic fat and IPFD were manually quantified by independent raters. Moderation analyses were performed with adjustment for sex and ethnicity. There were 367 participants included. Adjusted analyses of the overall cohort revealed that age, glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides were significant moderators (p < 0.05) of the association between hepatic fat and IPFD. Ranges of significance included age < 61 years, HbA1c < 45 mmol/mol, LDL-C < 157 mg/dL, HDL-C > 36 mg/dL, and triglycerides < 203 mg/dL. The association between hepatic fat and IPFD is generally present in young and middle-aged adults with good cardiometabolic health, whereas the link between the two fat depots becomes uncoupled in older adults or individuals with cardiometabolic risk factors.

Enhancing Intrapancreatic Fat Deposition and Pancreatitis Research With Additional Considerations

Enhancing Intrapancreatic Fat Deposition and Pancreatitis Research With Additional Considerations

Pancreatitis as a Matter of Fat: The Causal Role of High Intrapancreatic Fat Deposition.

Pancreatitis as a Matter of Fat: The Causal Role of High Intrapancreatic Fat Deposition.

The Causal Effect of Intrapancreatic Fat Deposition on Acute and Chronic Pancreatitis: A Mendelian Randomization Study.

Recent associative studies have linked intrapancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear. Using Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach used genetic variants from genomewide association studies of IPFD (n = 25,617), acute pancreatitis (n = 6,787 cases/361,641 controls), and chronic pancreatitis (n = 3,875 cases/361,641 controls). Genetically predicted IPFD was significantly associated with acute pancreatitis (odds ratio per 1-SD increase: 1.40 [95% CI: 1.12-1.76], P = 0.0032) and chronic pancreatitis (odds ratio: 1.64 [95% CI: 1.13-2.39], P = 0.0097). Our findings support a causal role of IPFD in pancreatitis, suggesting that reducing IPFD could lower the risk of pancreatitis.

Correlation between type 2 diabetes mellitus remission and intrapancreatic fat deposition.

Intrapancreatic fat deposition (IPFD) exerts a significant negative impact on patients with type 2 diabetes mellitus (T2DM), accelerates disease deterioration, and may lead to impaired β-cell quality and function. To investigate the correlation between T2DM remission and IPFD. We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023, including 40 patients with weight loss-induced T2DM remission (research group) and 40 patients with short-term intensive insulin therapy-induced T2DM remission (control group). We comparatively analyzed improvements in IPFD [differential computed tomography (CT) values of the spleen and pancreas and average CT value of the pancreas]; levels of fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and insulin; and homeostasis model assessment of insulin resistance (HOMA-IR) scores. Correlation analysis was performed to explore the association between T2DM remission and IPFD. After treatment, the differential CT values of the spleen and pancreas, FBG, 2hPBG, and HOMA-IR in the research group were significantly lower than those before treatment and in the control group, and the average CT value of the pancreas and insulin levels were significantly higher. Correlation analysis revealed that the greater the T2DM remission, the lower the amount of IPFD. T2DM remission and IPFD are inversely correlated.

Genetic Evidence for a Causal Link between Intra-Pancreatic Fat Deposition and Pancreatitis: a Mendelian Randomization Study.

Recent associative studies have linked intra-pancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear. Utilizing Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach utilized genetic variants from genome-wide association studies of IPFD (n=25,617), acute pancreatitis (n=6,787 cases/361,641 controls), and chronic pancreatitis (n=3,875 cases/361,641 controls). Genetically predicted IPFD was significantly associated with acute pancreatitis (OR per 1-SD increase: 1.40[95%CI:1.12-1.76], p=0.0032) and chronic pancreatitis (OR:1.64[95%CI:1.13-2.39], p=0.0097). Our findings support a causal role of IPFD in pancreatitis, suggesting that reducing IPFD could lower the risk of pancreatitis.

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

To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. 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. 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). 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.

The Pharmacological Landscape for Fatty Change of the Pancreas.

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.

Intra-pancreatic fat is associated with continuous glucose monitoring metrics.

To investigate the relationship of fat in the pancreas withtime spent in different glycaemic ranges. Abdominal magnetic resonance imaging at 3.0 Tesla was used to quantify fat in the pancreas as both continuous [i.e. intra-pancreatic fat deposition (IPFD)] and binary (i.e. fatty change of the pancreas vs. normal pancreas) variables. Dexcom G6 devices were used to collect continuous glucose monitoring data every 5 min over a continuous 7-day period. Time above range (TAR), time in range (TIR) and time below range were computed. Statistical models were built to adjust for age, sex, body composition, and other covariates in linear regression analysis and analysis of covariance. In total, 38 individuals were studied. IPFD was significantly associated with TAR (p = .036) and TIR (p = .042) after adjustment for covariates. For every 1% increase in IPFD, there was a 0.3 unit increase in TAR and a decrease in TIR. Individuals with fatty change of the pancreas, when compared with those with normal pancreas, had significantly higher TAR (p = .034) and lower TIR (p = .047) after adjustment for covariates. Neither IPFD (p = .805) nor fatty change of the pancreas (p = .555) was associated with time below range after adjustment for covariates. Increased fat in the pancreas is associated with excessive glycaemic variability. Fatty change of the pancreas may contribute to heightening the risk of cardiovascular diseases.

Abstract 1603: Intra-pancreatic fat promotes the progression of PDAC by activating thermogenesis

Abstract Background: The presence of minimal intra-pancreatic fat deposition (IPFD) in the healthy human pancreas has been demonstrated in numerous studies. But excess IPFD, or fatty pancreas disease, leads to a wide array of diseases, including but not limited to diabetes, pancreatitis, and pancreatic ductal adenocarcinoma (PDAC). Remarkably, PDAC patients with excessive intra-pancreatic fat accumulation are commonly associated with a poor prognosis compared to those with minimal deposition. However, the interaction between tumor and intra-pancreatic adipose tissue remains elusive. Here, we evaluated the pancreatic fat infiltration in normal people and patients with PDAC respectively, and explored the mechanism of how intra-pancreatic fat affects the progression of PDAC. Methods: Magnetic resonance imaging (MRI) and clinical biopsy specimens were used to assess the degree of pancreatic fat infiltration in PDAC patients and healthy control individuals. The C57BL/6J mice injected orthotopically with KPC cells and adipocytes, high-fat diet (HFD)-induced obesity KC (Pdx1-Cre; KrasLSL-G12D/WT) mice, and KC; ob/ob mice were established to dynamically observe how adipocytes affect tumor progression in vivo. The snRNA-seq of tumor samples and proteomics of conditional medium of PDAC cell lines were performed to identify the mechanism of interaction between cancer cells and adipocytes. Results: We found that patients with PDAC presented excess intra-pancreatic fat deposition more frequently than healthy individuals, and the degree of fat infiltration was positively correlated with the tumor burden of PDAC patients. HFD-induced obesity KC mice and KC; ob/ob mice showed a higher degree of IPFD, which contributed to tumor growth and low survival rates of mice. Additionally, the expression of uncoupling protein 1 was upregulated in PDAC patients and KPC (Pdx1-Cre; KrasLSL-G12D/WT; p53LSL-R172H/WT) mice compared to normal controls. Constantly, the snRNA-seq of PDAC samples demonstrated the increase in thermogenic signature. In vitro, C3H10T1/2 cells treated with conditional medium from pancreatic cancer cell lines or co-cultured with pancreatic cancer cell lines showed increased expression of browning markers and elevated oxygen consumption rate. Specifically, combined analysis of the proteomic of T3M4 and CFPAC-1 conditional medium and the snRNA-seq revealed that pancreatic cancer cells secreted integrin β4 (ITGB4) to improve the thermogenesis of intra-pancreatic adipocytes (IPA), which in turn promoted cancer cell progression. Conclusion: Parts of PDAC patients present excess intra-pancreatic fat accumulation, a process associated with tumor growth and poor prognosis. Mechanistically, pancreatic cancer cells activate the thermogenesis of IPA by secreting ITGB4, and then the thermogenetic adipocytes fuel the progression of the tumor in response. Citation Format: Xinpeng Yin, Yuan Chen, Ruiyuan Xu, Chenglin Hu, Chengcheng Wang, Yupei Zhao. Intra-pancreatic fat promotes the progression of PDAC by activating thermogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1603.

Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study

Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N= 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p<5×10-8) from a genome-wide association study in the UK Biobank (N= 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidencefor a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.

Intrapancreatic fat deposition is unrelated to liver steatosis in metabolic dysfunction-associated steatotic liver disease

Individuals with obesity may develop intrapancreatic fat deposition (IPFD) and fatty pancreas disease (FPD). Whether this causes inflammation and fibrosis and leads to pancreatic dysfunction is less established than for liver damage in metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, the interrelations of FPD and MASLD are poorly understood. Therefore, we aimed to assess IPFD and fibro-inflammation in relation to pancreatic function and liver disease severity in individuals with MASLD. Seventy-six participants from the Amsterdam MASLD-MASH cohort (ANCHOR) study underwent liver biopsy and multiparametric MRI of the liver and pancreas, consisting of proton-density fat fraction sequences, T1 mapping and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). The prevalence of FPD was 37.3%. There was a clear correlation between pancreatic T1 relaxation time, which indicates fibro-inflammation, and parameters of glycemic dysregulation, namely HbA1c (R= 0.59; p <0.001), fasting glucose (R= 0.51; p <0.001) and the presence of type 2 diabetes (mean 802.0ms vs. 733.6ms; p <0.05). In contrast, there was no relation between IPFD and hepatic fat content (R= 0.03; p=0.80). Pancreatic IVIM diffusion (IVIM-D) was lower in advanced liver fibrosis (p <0.05) and pancreatic perfusion (IVIM-f), reflecting vessel density, inversely correlated to histological MASLD activity (p <0.05). Consistent relations exist between pancreatic fibro-inflammation on MRI and endocrine function in individuals with MASLD. However, despite shared dysmetabolic drivers, our study suggests IPFD is a separate pathophysiological process from MASLD. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and 68% of people with type 2 diabetes have MASLD. However, fat infiltration and inflammation in the pancreas are understudied in individuals with MASLD. In this cross-sectional MRI study, we found no relationship between fat accumulation in the pancreas and liver in a cohort of patients with MASLD. However, our results show that inflammatory and fibrotic processes in the pancreas may be interrelated to features of type 2 diabetes and to the severity of liver disease in patients with MASLD. Overall, the results suggest that pancreatic endocrine dysfunction in individuals with MASLD may be more related to glucotoxicity than to lipotoxicity. NTR7191 (Dutch Trial Register).

Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches.

Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD.

Relationship of Liver Blood Tests and T1 Relaxation Time With Intra-pancreatic Fat Deposition

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. 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. 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). Elevated alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transferase are associated with increased IPFD. Hepatic fibrosis does not appear to be associated with IPFD.

Effects of liraglutide on intrapancreatic fat deposition in patients with type 2 diabetes

Ectopic fat deposition is associated with worsening of glycemic control. This study was conducted to determine whether liraglutide reduces ectopic fat deposition, especially in pancreas, in patients with type 2 diabetes (T2D). We retrospectively recruited T2D patients who underwent abdominal unenhanced CT scans both before and after administration of liraglutide (N=13) or glimepiride (N=29). Using CT values of pancreas (P), liver (L) and spleen (S), we defined the indices of intrapancreatic and liver fat as P-S value and L-S value, respectively. Increase of each value suggests the reduction of each fat deposition. The values of HbA1c (p=0.0017) and body weight (p=0.0081) decreased, and L-S (p=0.0024) increased significantly after administration of liraglutide compared with those at baseline. Similarly, P-S tended to increase in the liraglutide group (p=0.0547) and increased significantly in the liraglutide subgroup with fatty pancreas (p=0.0303), defined as having baseline P-S less than-5. In the glimepiride group, P-S did not increase regardless of baseline P-S. Among patients with fatty pancreas, administration of liraglutide tended to be a significant factor for the change in P-S after adjustment for the change in HbA1c (p=0.1090) and the change in visceral fat area (p=0.1030). Intrapancreatic fat deposition was decreased after treatment with liraglutide, but not glimepiride, in T2D patients with fatty pancreas. Liraglutide might reduce intrapancreatic fat deposition independently of decreases in HbA1c and visceral fat volume.

Comprehensive analysis of dyslipidemia states associated with fat in the pancreas

BackgroundThe global burden of cardiovascular diseases continues to rise, and it is increasingly acknowledged that guidelines based on traditional risk factors fail to identify a substantial fraction of people who develop cardiovascular diseases. Fat in the pancreas could be one of the unappreciated risk factors. This study aimed to investigate the associations of dyslipidemia states with fat in the pancreas. MethodsAll participants underwent magnetic resonance imaging on the same 3.0 T scanner for quantification of fat in the pancreas, analyzed as both binary (i.e., fatty change of the pancreas) and continuous (i.e., intra-pancreatic fat deposition) variables. Statistical analyses were adjusted for body mass index, glycated hemoglobin, fasting insulin, ethnicity, age, and sex. ResultsThere were 346 participants studied. On most adjusted analyses, high-density lipoprotein cholesterol dyslipidemia was significantly associated with both fatty change of the pancreas (p = 0.010) and intra-pancreatic fat deposition (p = 0.008). Neither low-density lipoprotein cholesterol dyslipidemia nor triglyceride dyslipidemia were significantly associated with fatty change of the pancreas and intra-pancreatic fat deposition. The absence of any dyslipidemia was inversely associated with both fatty change of the pancreas (p = 0.016) and intra-pancreatic fat deposition (p < 0.001). ConclusionsDyslipidemias are uncoupled when it comes to the relationship with fat in the pancreas, with only high-density lipoprotein cholesterol dyslipidemia having a consistent and strong link with it. The residual cardiovascular diseases risk may be attributed to fatty change of the pancreas.

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.

Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study.

Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was therefore to examine the association between circulating abundances of candidate miRNAs, IPFD and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Asian Chinese (n = 34; BMI = 26.7 ± 4.2 kg/m2) and European Caucasian (n = 34; BMI = 28.0 ± 4.5 kg/m2) females from the TOFI_Asia cohort underwent MRI and MRS analysis of pancreas (MR-%IPFD) and liver fat (MR-%liver fat), respectively, to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with IPFD and liver fat deposition were quantified by qRT-PCR. miR-21-3p and miR-320a-5p correlated with MR-%IPFD, plasma insulin and HOMA2-IR, but not MR-%liver fat. MR-%IPFD remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%IPFD, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for a wider application as a specific circulatory correlate of IPFD.

Remnant cholesterol, but not low-density lipoprotein cholesterol, is associated with intra-pancreatic fat deposition.

To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD). All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition. A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD. Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.