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![Dietary and adipose fat composition and parameters of local, systemic severity of CER pancreatitis in UFA-and SFA-fed ob/ob mice. (A1) Table comparing the fatty acid composition of fat pad triglycerides (TG) and diets of mice given the SFA-and UFA-enriched diets. Body weights (A2), body fat (A3), and body fat as a percentage of body weight (A4) in the SFA-and UFA-fed mice. Serum amylase (B1) and lipase (B2) in control (CON) mice and after 24 hours of AP (CER). Local pancreatic injury seen histologically (C1) and quantified as acinar necrosis (C2) as a percentage of total parenchymal area and percentage of acinar necrosis adjacent to the FN (shown in yellow rectangles), termed as "% peri-fat acinar necrosis" (C3). Systemic injury measured as renal injury [TUNEL staining showing brown nuclei in (D1) and serum BUN in (D2)], lung TUNEL positivity highlighted with arrows in (D3), and shown as number per high-power field (HPF) in (D4), along with shock (as measured by a drop in carotid pulse distention) in (E1), serum calcium (E2), and survival curve (E3) of mice with CER AP. NS, not significant.](publication/348886163/figure/fig2/AS:994578094108673@1614137304792/Dietary-and-adipose-fat-composition-and-parameters-of-local-systemic-severity-of-CER.png)
Dietary and adipose fat composition and parameters of local, systemic severity of CER pancreatitis in UFA-and SFA-fed ob/ob mice. (A1) Table comparing the fatty acid composition of fat pad triglycerides (TG) and diets of mice given the SFA-and UFA-enriched diets. Body weights (A2), body fat (A3), and body fat as a percentage of body weight (A4) in the SFA-and UFA-fed mice. Serum amylase (B1) and lipase (B2) in control (CON) mice and after 24 hours of AP (CER). Local pancreatic injury seen histologically (C1) and quantified as acinar necrosis (C2) as a percentage of total parenchymal area and percentage of acinar necrosis adjacent to the FN (shown in yellow rectangles), termed as "% peri-fat acinar necrosis" (C3). Systemic injury measured as renal injury [TUNEL staining showing brown nuclei in (D1) and serum BUN in (D2)], lung TUNEL positivity highlighted with arrows in (D3), and shown as number per high-power field (HPF) in (D4), along with shock (as measured by a drop in carotid pulse distention) in (E1), serum calcium (E2), and survival curve (E3) of mice with CER AP. NS, not significant.
Source publication
Obesity sometimes seems protective in disease. This obesity paradox is predominantly described in reports from the Western Hemisphere during acute illnesses. Since adipose triglyceride composition corresponds to long-term dietary patterns, we performed a meta-analysis modeling the effect of obesity on severity of acute pancreatitis, in the context...
Contexts in source publication
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... averaged 45.5 ± 0.5 g in both groups. CER AP reduced survival to 10% in the UFA group by day 3 versus 90% in the SFA group (P < 0.02; fig. S6). We then simulated the lower cutoff BMI (≤25) associated with SAP in countries with a higher %UFA intake. AP was initiated in UFA-fed mice weighing 20 to 30% less and having 35 to 40% less adipose tissue (Fig. 2, A2 to A4). AP increased serum amylase and lipase similarly in both groups (Fig. 2, B1 and B2) but was worse in the leaner UFA group. The SFA group has lesser pancreatic necrosis (5.8 ± 0.8 versus 16.8 ± 4.7%, P = 0.024; Fig. 2, C1 and C2) especially bordering FN, termed peri-fat acinar necrosis (2.7 ± 0.4 versus 6.9 ± 1.6%, P = 0.03; ...
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... a higher %UFA intake. AP was initiated in UFA-fed mice weighing 20 to 30% less and having 35 to 40% less adipose tissue (Fig. 2, A2 to A4). AP increased serum amylase and lipase similarly in both groups (Fig. 2, B1 and B2) but was worse in the leaner UFA group. The SFA group has lesser pancreatic necrosis (5.8 ± 0.8 versus 16.8 ± 4.7%, P = 0.024; Fig. 2, C1 and C2) especially bordering FN, termed peri-fat acinar necrosis (2.7 ± 0.4 versus 6.9 ± 1.6%, P = 0.03; green outline, Fig. 2, C1 and C3). Consistent with SAP (53, 54), the UFA-fed mice had greater lung and renal tubular TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) positivity, ...
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... to A4). AP increased serum amylase and lipase similarly in both groups (Fig. 2, B1 and B2) but was worse in the leaner UFA group. The SFA group has lesser pancreatic necrosis (5.8 ± 0.8 versus 16.8 ± 4.7%, P = 0.024; Fig. 2, C1 and C2) especially bordering FN, termed peri-fat acinar necrosis (2.7 ± 0.4 versus 6.9 ± 1.6%, P = 0.03; green outline, Fig. 2, C1 and C3). Consistent with SAP (53, 54), the UFA-fed mice had greater lung and renal tubular TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) positivity, higher serum blood urea nitrogen (BUN) levels (Fig. 2, D1 to D4), a greater decrease in carotid pulse distention (consistent with ...
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... transferase-mediated deoxyuridine triphosphate nick end labeling) positivity, higher serum blood urea nitrogen (BUN) levels (Fig. 2, D1 to D4), a greater decrease in carotid pulse distention (consistent with shock), and SAP-associated hypocalcemia (55, 56) (Fig. 2, E1 and E2), resulting in 20% survival (P < 0.02 versus 90% in the SFA group; Fig. 2E3). The findings of SAP were replicated in UFA-fed C57BL6 mice with diet-induced obesity (DIO), but not the normal chow-fed mice (30.8 ± 0.7 g), which had mild pancreatitis ( fig. S7, A to F) (27). However, we did not use DIO as the primary model since the time to weight gain (>5 months) was ...
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... UFA mice had a larger cytokine mRNA increase in the fat pads during AP and interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- (TNF-) proteins in the sera (Fig. 3, C1 to C4), which correlated with lower IB- (42 ± 15% of controls, P < 0.05) in the necrosed UFA fat pads (Fig. ...
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... (LA-OA-PA), and compared these to GTL (LA-LA-LA). Palmitate disproportionately reduced lipolysis over 15 min. For example, LLP generated <30% LA, and PLP generated <9% LA versus GTL (Fig. 5B1). Both linoleate (4.3 ± 1 M) and oleate (4.4 ± 1.2 M) generation were markedly reduced on LOP. This was paralleled by reductions in m and Cai increase (Fig. 5, B2 and ...
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... a distance of 4.04 Å between the hydroxyl group of Ser 152 and the carbonyl C atom of the triglyceride's glycerol backbone (Fig. 5D1). LLP docked with a GlideScore of −4.72 kcal/mol at a distance of 9.99 Å from Ser 152 , and LOP and GTP respectively produced GlideScores of −1.33 and −1.58 while being 12.42 and 11.98 Å from the catalytic serine (Fig. 5, D2 to D4). To verify the integrity of the docking simulation, the ligand present in the 1LPA crystal structure (61), dilauryl phosphatidyl choline (DLPC), was removed and then docked with the same induced fit docking protocol used for the three triglycerides. DLPC docked with a GlideScore of −7.46 ( fig. S14A) and at a distance of 3.59 Å ...
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... of visceral fat more prone to lipolysis (Figs. 2 and 3), generating higher concentrations of monomeric NEFA (Fig. 6), thus worsening outcomes in leaner populations (Fig. 1). The reverse holds true for SFAs, and this is relevant to studies from Western countries (72) that show AP severity to be independent of intra-abdominal fat amounts even when this fat is above the range in studies from Asian countries (71). ...
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... enantiopure form. While this remains beyond our scope, the previous findings that pancreatic lipase hydrolyzes triglyceride without any stereoselectivity for the sn-1 or sn-3 position (59) suggest that the interference by palmitate is independent of these locations on the glycerol backbone. Last, the mechanisms underlying the exothermic changes (Fig. 5, C2 and C3) following the initial interaction of PNLIP and triglycerides remain unclear. The relative magnitude of these, i.e., GTL > LLP > LOP, mirror the initial interaction. Previous studies suggest that this may be due to binding of the generated LA to aromatic residues on PNLIP and further increasing its activity ...
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... explore the impact of BMI on AP severity, we conducted a literature review by searching the PubMed database from inception to January 2017). The terms "BMI" or "obese" and "acute pancreatitis" as well as "severe" or "severity" were used. A total of 118 studies were retrieved, as shown ( fig. S2). Seventy-nine studies were excluded, as they were not related to the subject of this review, as were 12 studies that were reviews/meta-analyses/hypotheses. The remaining studies were extensively reviewed for eligibility criteria, which were as follows: (i) clear BMI cutoff to define obesity, (ii) clear report of the incidence of mild ...
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... was divided into MAP and SAP and then into those that were obese versus nonobese. In cases where this was not explicitly clear, the communicating author was contacted (30,45), and the numbers so provided were included in the study. Papers that did not have adequate data or for reasons mentioned in the last column of fig. S1 and detailed in fig. S2 were excluded from the meta-analysis (n = 7). When more than one BMI cutoff was mentioned, the BMI used was the one at which the SAP risk ...
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Citations
... It is known that FFAs are of two types based on the presence or absence of C-C double bonds: 1) saturated fatty acids (SFA) and 2) unsaturated fatty acids (UFA). Dietary unsaturated/saturated components determine the fatty acid composition in fat cell triglyceride, affecting AP severity [58]. Cellular excess long-chain SFA is considered to be associated with lipotoxicity [59]. ...
... Oleic acid has been found to be the most abundant FFA found in pancreatic necrotic collections [63]. UFA produce higher levels of FFA as they are more easily lipolysis by pancreatic lipase [57,58]. The better aqueous UFA stability helps them exist as monomers at higher concentrations than SFA, resulting in lipotoxic inflammation and organ failure [58,64]. ...
... UFA produce higher levels of FFA as they are more easily lipolysis by pancreatic lipase [57,58]. The better aqueous UFA stability helps them exist as monomers at higher concentrations than SFA, resulting in lipotoxic inflammation and organ failure [58,64]. notably, UFA caused a sudden release of intracellular calcium, inhibition of mitochondrial complexes I and V, upregulation of inflammatory mediators and acinar necrosis causes acute pancreatitis [65]. ...
It is well known, that the inflammatory process that characterizes acute pancreatitis (AP) can lead to both pancreatic damage and systemic inflammatory response syndrome (SIRS). During the last 20 years, there has been a growing incidence of episodes of acute pancreatitis associated with hypertriglyceridaemia (HTAP). This review provides an overview of triglyceride metabolism and the potential mechanisms that may contribute to developing or exacerbating HTAP. The article comprehensively discusses the various pathological roles of free fatty acid, inflammatory response mechanisms, the involvement of microcirculation, serum calcium overload, oxidative stress and the endoplasmic reticulum, genetic polymorphism, and gut microbiota, which are known to trigger or escalate this condition. Future perspectives on HTAP appear promising, with ongoing research focused on developing more specific and effective treatment strategies.
... Pancreatic lipases can induce the lipolysis of adipocyte triglycerides to non-esterified free fatty acids (NEFA). Unsaturated fatty acids (UFAs) induce acinar cell injury, promotes local pancreatic injury and mediates lipotoxicity as well as progression to multisystem organ failure [12][13][14][15]. Obesity results in a low-grade pro-inflammatory state, and more pro-inflammatory cytokines are activated in AP [16][17][18][19]. ...
Obese people with acute pancreatitis (AP) have an increased risk of developing severe acute pancreatitis (SAP), which prolongs the length of hospital stay and increases mortality. Thus, elucidation of the mechanisms through which SAP occurs in obese individuals will provide clues for possible treatment targets. Differences in early events in obese or lean patients with AP have not been conclusively reported. We selected C57BL/6 mice as lean mice models, ob/ob mice or diet induced obese (DIO) mice as obese mice models and then induced experimental AP in mice via injections of caerulein. There were suppressed p-AMPK expressions in the pancreas of obese mice, compared with same-age lean C57BL/6 mice, which were further reduced in AP mice models. Obese AP mice were treated using AICAR, a direct AMPK agonist, which prevented pancreatic damage and cell death, suppressed pancreatic enzyme levels in serum, reduced the areas of fat saponification in the peritoneal cavity, prevented injury in other organs and decreased mice mortality rate. Further assays showed that AICAR activates p-AMPK to stabilize pro-caspase-8. Pro-caspase-8 enhances RIPK3 degradation, inhibits pancreatic acinar cell necroptosis, and downregulates the release of pancreatic enzymes. Thus, activation of AMPK by AICAR alleviates pancreatic acinar cell necroptosis and converts SAP to mild acute pancreatitis in obese mice.
... 31 Studies have highlighted stark racial differences in the epidemiology of AP as ethnic minorities usually tend to have a greater degree of severity of AP and are associated with an increased risk of adverse outcomes. 21,[32][33][34][35] These subset populations may have less access to education, less access to healthcare, and diminished healthcare coverage, which often leads to a delayed presentation, development of complications, and a more severe clinical course of the disease. 21 Literature reports that Black populations have 2-3 times greater risk of hospitalization secondary to AP compared with their White counterparts. ...
... 21,[32][33][34][35] These subset populations may have less access to education, less access to healthcare, and diminished healthcare coverage, which often leads to a delayed presentation, development of complications, and a more severe clinical course of the disease. 21 Literature reports that Black populations have 2-3 times greater risk of hospitalization secondary to AP compared with their White counterparts. [32][33][34] Blacks have also been noted to have higher rates of readmissions of AP after the index episode. ...
Objective:
To identify the influence of body mass index (BMI) on Acute Pancreatitis (AP) hospitalizations in the United States (US).
Methods:
The National Inpatient Sample was utilized to identify normal weight, overweight and obese AP hospitalizations in the US from 2016-2019 based on BMI. Hospitalization characteristics and outcomes were compared.
Results:
Between 2016-2019, there were 314,215 (74.7%) obese, 27,005 (6.4%) overweight and 79,380 (18.9%) normal weight AP hospitalizations. Obese AP hospitalizations were younger (51.5 vs 56.5 years, p < 0.0001) compared to the normal weight cohort. However, normal weight AP hospitalizations had a higher proportion of Blacks and Asians compared to the obese subgroup. We also noted a higher all-cause inpatient mortality for normal weight AP hospitalizations (3.4% vs 2.8% vs 1.8%, p < 0.0001) compared to the overweight and obese cohorts, respectively. Furthermore, normal weight AP hospitalizations had a higher proportion of patients with pancreatic pseudocyst formation and pancreatic necrosis compared to the overweight and obese cohorts. The mean length of stay (5.8 vs 8.2 days, p < 0.0001) and mean total healthcare costs ($66,742 vs $82,319, p < 0.0001) were lower for obese compared to normal weight AP hospitalizations.
Conclusions:
Normal weight AP hospitalizations had higher inpatient mortality and complications compared to obese hospitalizations.
... Hypertriglyceridemia is the third most common cause of AP [13], and clinically, triglyceride-related metabolites are positively associated with the severity of AP [14,15] and pancreatic injury [16]. Lipotoxicity affects not only the multisystem organ failure of AP [17] but also regeneration after AP [18], and lipid saturation is also associated with lipotoxic systemic inflammation [19]; therefore, it is important to identify the lipids involved in the development of AP. We previously reported obviously changed phosphoglycerides and polyunsaturated fatty acyls are probably going to play an important role in the pathogenesis of a cerulein-induced AP mouse model [20]. ...
... In the positive mode, we detected a total of 487 lipids belonging to 8 different lipid subclasses. These included 21 PE-Ps, 19 Figure 4A and Table S6). Figure 4B demonstrates that the analytical process for screening changed representative lipids related to the Orn-SAP procession in the serum. ...
The relationship between the type and intensities of lipids of blood and pancreas and the pathological changes in the pancreas during severe acute pancreatitis (SAP) remains unclear. In our study, we employed a rat model of SAP induced through intraperitoneal ornithine injections. We collected serum and pancreas samples at various time points (0–144 h) for histopathological and biochemical assessments, followed by lipidomic analyses using LC-MS/MS or in situ mass spectrometry imaging (MSI) To discern changes over time or at specific points, we employed time-course and univariate analyses for lipid screening, respectively. Our findings indicated that the peak inflammation in the Orn-SAP model occurred within the 24–30 h timeframe, with evident necrosis emerging from 24 h onwards, followed by regeneration starting at 48 h. Time-course analysis revealed an overall decrease in glycerophospholipids (PEs, PCs, LPEs, LPCs), while CEs exhibited an increase within the pancreas. Univariate analysis unveiled a significant reduction in serum TAGs containing 46–51 carbon atoms at 24 h, and CERs in the pancreas significantly increased at 30 h, compared with 0 h. Moreover, a substantial rise in TAGs containing 56–58 carbon atoms was observed at 144 h, both in serum and pancreas. MSI demonstrated the CERs containing saturated mono-acyl chains of 16 and 18 carbon atoms influenced pancreatic regeneration. Tracing the origin of FFAs hydrolyzed from pancreatic glycerophospholipids and serum TAGs during the early stages of inflammation, as well as FFAs utilized for CEs and CERs synthesis during the repair phase, may yield valuable strategies for diagnosing and managing SAP.
... 5,6 However, previous studies have generated conflicting results: some even suggested the "obesity paradox," implying that obesity has protective effects in severe AP, 7 while others found that obesity does not increase the risk of organ failure. 8 Results regarding the impact of alcoholic etiology on AP outcomes have similarly been mixed. 9 This heterogeneity is largely attributable to significant methodologic constraints that plague both prospective observational studies and retrospective cohort studies that use large administrative databases. ...
... This is the largest prospective observational study in AP that pro- Although obesity has emerged as an important prognostic factor in several acute inflammatory illnesses, including sepsis and COVID-19, 5,16 AP literature has shown mixed results on whether obesity increases the risk of MSOF. 8,11 Most studies analyzed BMI as a dichotomized variable, which simplifies the interpretation of results but also increases the vulnerability to potential confounders and bias. 15 found that the increased risk of death among obese COVID-19positive subjects was seen exclusively among male subjects. ...
Background:
Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF.
Objective:
We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP.
Methods:
A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex.
Results:
Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05).
Conclusion:
Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.
... explained the obesity paradox in their article by suggesting that different visceral triglyceride saturation status could have varying effects on AP severity [51]. According to the results of the subgroup analysis in this meta-analysis, mean age of patients appears to have an effect on adiposity factors and resultantly affects AP severity, which may provide a new thought for the obesity paradox. ...
Background Severe acute pancreatitis (SAP) is a dangerous condition with a high mortality rate. Many studies have found an association between adipokines and the development of SAP, but the results are controversial. Therefore, we performed a meta-analysis of the association of inflammatory adipokines with SAP.
Methods We screened PubMed, EMBASE, Web of Science and Cochrane Library for articles on adipokines and SAP published before March 2, 2023. The quality of the literature was assessed using QUADAS criteria. Standardised mean differences (SMD) with 95% confidence intervals (CI) were calculated to assess the combined effect. Subgroup analysis, sensitivity analysis and publication bias tests were also performed on the information obtained.
Result Fifteen eligible studies included 936 patients with acute pancreatitis (AP). Pooled analysis showed that patients with SAP had significantly higher levels of circulating resistin (SMD = 0.55, 95% CI:0.15 to 0.94, z = 2.70, P = 0.007). The difference in circulating leptin and adiponectin levels between SAP and MAP patients was not significant (SMD = 0.31, 95% CI: -0.11 to 0.73, z = 1.44, P = 0.149 and SMD = -0.07, 95% CI: -0.30 to 0.16, z = 0.57, P = 0.570). Subgroup analyses identified mean age of the patients as possible sources of circulating resistin level heterogeneity.
Conclusion Elevated levels of circulating resistin levels are associated with the development of SAP. Resistin may be potential biomarkers and therapeutic targets for SAP. However, the age of the patient may influence these results.
... Western blotting was also performed using standard methods. 23 After protein denaturation, 20 μg of extracted protein was fractionated on a 10% SDS-PAGE gel and then transferred to a polyvinylidene fluoride (PVDF) membrane with a 0.45-mm pore size (Millipore, MA, USA). The membranes were then blocked in 5% milk at room temperature for 1 h, washed by TBST (Beyotime, Jiangsu, China) and incubated overnight on a shaker at 4°C for the primary antibody. ...
Purpose:
Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10-gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism.
Methods:
The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities.
Results:
In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel.
Conclusion:
This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.
... 129 This entry can result from the concurrent release of phospholipases and be exacerbated by FA-induced adipocyte damage. 129 The resulting interaction between lipase and TG can cause fat necrosis of the involved adipocytes [129][130][131][132] and adipocyte receptor-associated TG release. This release, which may be mediated via G-protein coupled protease-activated receptor 4, 133 is triggered proteolytically by trypsin. ...
... 137 Recently, it was demonstrated that the dietary unsaturated/saturated composition determines the FA composition in adipocyte TG, which in turn can influence AP severity. 131 Unsaturated long-chain FAs in a TG make it more prone to lipolysis by pancreatic lipase, whereas saturated long-chain FAs in a TG interfere with this interaction. 131 Therefore, an unsaturated TG may be hydrolyzed more and generate more NEFAs than a saturated TG. ...
... 131 Unsaturated long-chain FAs in a TG make it more prone to lipolysis by pancreatic lipase, whereas saturated long-chain FAs in a TG interfere with this interaction. 131 Therefore, an unsaturated TG may be hydrolyzed more and generate more NEFAs than a saturated TG. Moreover, unsaturated long-chain NEFAs are more aqueous stable than saturated ones. ...
Hypertriglyceridaemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important aetiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG‐induced AP and the clinically observed effects of HTG on outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG‐induced AP or AP in the presence of HTG and determining possible treatments are needed.
... Unsaturated fatty acids (UFA) induces acinar cell injury, promotes local pancreatic injury and mediates lipotoxicity as well as progression to multisystem organ failure [13][14][15][16] . Obesity results in a low-grade proin ammatory state, and more pro-in ammatory cytokines are activated during AP [17][18][19][20] . ...
Obese people with acute pancreatitis(AP) have an increased risk of developing severe acute pancreatitis (SAP), which prolongs the length of hospital stay and increases mortality. Thus, elucidation of the mechanisms through which severe acute pancreatitis occurs in obese individuals will provide clues for possible treatment targets. Differences in early events in obese or lean patients with acute pancreatitis have not been conclusively reported. We selected C57BL/6 mice as lean mice models, ob/ob mice or diet induced obese (DIO) mice as obese mice models and then induced experimental AP in mice via injections of caerulein. There were suppressed p-AMPK expressions in the pancreas of obese mice, compared with same age lean C57BL/6 mice, which were further reduced in AP mice models. Obese AP mice were treated using AICAR, a direct AMPK agonist, which prevented pancreatic damage and cell death, suppressed pancreatic enzyme levels in serum, reduced the areas of fat saponification in the peritoneal cavity, prevented injury in other organs and decreased mice mortality rate. Further assays showed that AICAR activates p-AMPK to stabilize pro-caspase-8. Pro-caspase-8 enhances RIPK3 degradation, inhibits pancreatic acinar cell necroptosis and downregulates the release of pancreatic enzymes. Thus, activation of AMPK by AICAR alleviates pancreatic acinar cell necroptosis and converts SAP to mild acute pancreatitis (MAP) in obese mice.
... La señalización continúa e interfiere principalmente con el factor de transcripción lipogénico (PPAR ) y en la proteína que regula los esteroles (SREBP-Ic). Esto hace comprender cómo es que la leptina al incrementar la actividad del AMP-Kinasa (AMP-K) disminuye la activación de la expresión de las enzimas lipogénicas malonil CoA carboxilasa y sintetasa de los AGL "efecto antiestatóico", en otras palabras, bloquea la enzima que sintetiza triglicéridos y ácidos grasos 24 . Al ser disminuido el efecto de los AGL por la leptina, se incrementa la expresión de CoA oxidasa y Carnitil-palmitoil transferasa (CPT-1) enzimas clave en la adecuada oxidación de ácidos grasos en la matriz mitocondrial, lo que hace a la leptina una hormona liporeguladora 25 . ...
Resumen Introducción. La diabesidad es el concepto para describir la ocurrencia de la diabetes y la obesidad de forma simultánea. En el mundo, cada día aumentan las cifras de personas con esta condición y se espera un crecimiento aún más elevado para años futuros, lo cual puede ser catastrófico para la salud individual, salud pública, economía y sistemas sanitarios. Desarrollo. Para comprender el fenómeno de la diabesidad se deben analizar diferentes factores. En este ensayo se plantean dos teorías con las que se puede dar sustento al desarrollo del padecimiento: Teoría del gen ahorrador de energía y desarrollo de genes sociales en el medio obesogénico. Conclusión. La diabesidad es un fenómeno complejo, multi-etiológico, basado en la influencia de las condiciones fisiológicas individuales y las condiciones del contexto social. Palabras clave: obesidad, diabetes, determinantes sociales de la salud. Abstract Introduction. Diabesity is when both diabetes and obesity occur simultaneously. Around the world, the number of people with diabesity is rising every day, and an even steeper climb is expected in the future. This growth in diabesity could have a detrimental effect on both the economy as well as personal health, public health, and healthcare systems. To fully understand the diabesity phenomenon, different factors should be analyzed. In this thesis, two theories will be presented to explain how the disease is manifested: the energy efficiency gene theory, and the social genes theory which will delve into how such genes are developed in an obesogenic environment. Conclusion. Diabesity is a complex, multi-etiological phenomenon, that stems from individual physiological conditions and conditions in the social context.
