Association of serum NOD-like receptor protein 3 levels with impaired fat tolerance and hypertriglyceridemia.

The NOD-like receptor protein 3 (NLRP3) inflammasome plays a key role in lipid metabolism. We used an oral fat tolerance test (OFTT) to detect whether serum NLRP3 levels differed in people with different fat tolerances and evaluate whether NLRP3 was associated with impaired fat tolerance (IFT) and hypertriglyceridemia (HTG). We performed the OFTT using 176 volunteers. The groups were divided according to fasting and postprandial triglyceride (TG) levels: 1) normal fat tolerance (NFT) group (TG at 0 h <1.7 mmol/L and TG at any time point <2.5 mmol/L); 2) IFT group (TG at 0 h <1.7 mmol/L and TG at any time point >2.5 mmol/L); and 3) HTG group (TG at 0 h ≥1.7 mmol/L). With decreased lipid tolerance, the TG and NLRP3 levels increased gradually before a high-fat meal and at any time point after 0 h. NLRP3 levels reached a peak 2 h after meal consumption in all three groups. After adjustment for confounding indicators, logistic regression analysis revealed that fasting serum NLRP3 levels were positively associated with both IFT and HTG (for IFT, odds ratio [OR]: 1.079 [1.037-1.123], p < 0.001; for HTG, OR: 1.085 [1.049-1.123], p < 0.001). According to the receiver operating characteristic curve, fasting serum NLRP3 levels were an effective biomarker for IFT and HTG diagnosis. These results indicate that the fasting serum NLRP3 is an independent risk factor for IFT and HTG, and is a valuable indicator for the early diagnosis of IFT and HTG.

Efficacy and safety of dapagliflozin combined with insulin in overweight or obese individuals with type 2 diabetes.

To investigate the efficacy and safety of dapagliflozin plus insulin in overweight or obese individuals with type 2 diabetes, from January to June 2019, 85 patients with type 2 diabetes were treated at Harrison International Peace Hospital and were randomized to either a combination group (43 cases) or a control group (42 cases). The control group received insulin, whereas the combination group additionally received dapagliflozin. On the first, second, fifth and tenth days, insulin doses and the time taken for standardized blood glucose were documented and their effectiveness and safety were compared. The time taken for standard insulin in the combination group was shorter vs. control group [(4.32±0.41) d vs. (6.93±0.57) d] and the difference in the dosage of insulin statistically significant (all P<0.05); there were significant differences in fasting blood glucose (FPG), 2h postprandial blood glucose (2hPBG) and hemoglobin a1c (HbA1c), fasting serum insulin (FINS) and homeostatic model assessment of beta (HOMA-ß) between the two groups and within the two groups (all P<0.05); the incidence of adverse reactions was lower in the combination grou [4.65% (2/43) vs. 11.90% (6/42)] (P<0.05). Dapagliflozin plus insulin improves blood glucose and islet ß cell activity with a good safety profile in overweight or obese individuals with type 2 diabetes.

Pterostilbene, a Resveratrol Derivative, Improves Ectopic Lipid Deposition in the Kidneys of Mice Induced by a High-Fat Diet.

BACKGROUND: Diabetic kidney disease is a major cause of global end-stage renal diseases. Ectopic lipid deposition in the renal tissues of diabetic kidney disease is one major factor leading to renal fibrosis and chronic kidney disease. Pterostilbene has been reported to display lipid-lowing activity and participate in many kidney diseases. However, the influence of pterostilbene on the ectopic lipid deposition is unclear. We intend to explore the influence of pterostilbene on the ectopic lipid deposition in the kidneys of mice induced by high fat. METHODS: A high-fat diet-induced diabetic mouse model was established to detect the alleviative effect of pterostilbene on the ectopic lipid deposition in the kidneys of diabetic mice. A biochemical analysis was performed to examine the levels of urine albumin, urine creatinine, serum creatinine, and blood urea nitrogen in mice after pterostilbene treatment. Histological analysis was conducted to detect the degree of renal injury and fibrosis. Oil red O staining and immunohistochemical staining were carried out to evaluate lipid droplets and the expression of adipose differentiation-related protein in renal tissues of the mice treated by pterostilbene. The protein levels were assessed by Western blotting. RESULTS: Pterostilbene inhibits the expression of the TGF-ß1 and p-smad3 and suppresses the protein levels of SREBP-1 and FAS, and it ultimately reduces the ectopic lipid deposition, alleviates the renal tubular damage and renal fibrosis in the kidneys of diabetic mice induced by high fat, and improves kidney function. CONCLUSION: Pterostilbene alleviates renal fibrosis and ectopic lipid deposition in the kidneys of diabetic mice induced by high-fat diet by inhibiting the TGF-ß1/smad3 signaling.

Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT). Patients and methods: In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed. Results: Serum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403). Conclusion: Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.

Serum Gamma Glutamyltransferase: A Biomarker for Identifying Postprandial Hypertriglyceridemia.

Purpose: Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG. Patients and Methods:  For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed. Results: The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG. Conclusion: Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.

Serum Fibroblast Growth Factor 21 Level After an Oral Fat Tolerance Test is Related to Postprandial Free Fatty Acid Level.

Purpose: The relationship between blood lipids and fibroblast growth factor (FGF) 21 in the postprandial period remains unclear. To investigate this, we observed the changes in blood lipid levels after an oral fat tolerance test (OFTT) and examined the short-term effects on FGF21. Patients and Methods: A total of 158 non-diabetic adult volunteers who underwent OFTT were randomly recruited from the Hebei General Hospital. Participants were stratified into three groups according to fasting and 4-h postprandial triglyceride levels: normal fat tolerance (NFT), impaired fat tolerance (IFT), and hypertriglyceridemia (HTG). Blood samples were collected at 2-h intervals for 6 h. Circulating total cholesterol levels, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, free fatty acids (FFA), and FGF21 were assessed. Results: Fasting FGF21 levels increased progressively in the NFT, IFT, and HTG groups and were strongly correlated with FFA levels (r = 0.531, P < 0.001). During the OFTT, the FFA and FGF21 levels decreased and then increased after reaching a nadir at 2 and 4 h, respectively. After adjusting for potential risk factors, the FFA incremental area under the curve (iAUC) was an independent influencing factor of FGF21 iAUC (P = 0.005). Conclusion: Fasting FGF21 levels showed a strong positive correlation with FFA. During OFTT, changes in FGF21 levels were closely associated with alterations in FFA exogenously changed by OFTT. Moreover, they were linearly related to each other. Therefore, the serum FGF21 level is positively correlated to the FFA level in the postprandial period.

Resveratrol ameliorates diabetic kidney injury by reducing lipotoxicity and modulates expression of components of the junctional adhesion molecule-like/sirtuin 1 lipid metabolism pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, and previous studies have shown that lipid deposits in the kidneys can lead to diabetic kidney damage. Resveratrol reduces circulating glucose and lipid concentrations, but it is unknown whether it can reduce renal lipid deposition and lipotoxic damage by regulating local lipid metabolism. We first showed that abnormal lipid metabolism is closely related to DKD in patients. There were excessive lipid deposits in the kidneys of patients with various stages of DKD, alongside abnormal expression of the junctional adhesion molecule-like (JAML)/sirtuin 1 (Sirt1) lipid synthesis pathway (P < 0.05). Next, we fed C57BL/6J mice a high-fat diet for 12 weeks, which caused an increase in body mass, blood glucose concentration, and blood lipid concentrations; and abnormalities in renal function (P < 0.05). Resveratrol administration ameliorated the defects in circulating lipid and glucose concentrations, renal dysfunction, the renal expression of components of the JAML/Sirt1 lipid synthesis pathway, and the expression of the adipose differentiation-related protein in the mice (P < 0.05). Histological staining also showed less lipid deposition and kidney damage. Thus, resveratrol regulates the JAML/Sirt1 lipid synthesis pathway, reduces lipid deposition in the kidney, and ameliorates diabetic kidney damage.