Fatty acid binding protein 4 (FABP4) and metabolic-related parameters in systemic lupus erythematosus active and non-active episode.

OBJECTIVE: To assess serum FABP4 and other metabolic-related parameters in Systemic Lupus Erythematosus (SLE) active and non-active episode. METHODS: Fifty-four SLE patients in Hasan Sadikin General Hospital, Bandung, Indonesia in 2018-2019 were recruited and serum samples were collected in their active and non-active episode status. Serum was analyzed for FABP4, leptin, glucose, and triglycerides. The clinical characteristics were analyzed from medical records. Disease activity was assessed with the SLEDAI-2K (≥4 defined as an active; <4 as non-active episode). RESULTS: Significantly correlation of Systolic Blood Pressure (SBP) (p = 0.001, r = 0.59) and C3 (p = 0.04, r = 0.47) between active and non-active episode. In non-active episode, there was significant correlation of FABP4 with Diastolic Blood Pressure (DBP) (p = 0.04, r = 0.26) and blood glucose (p = 0.01, r = -0.39). In active episode, there was significant correlation FABP4 with SBP (p = 0.04, r = -0.28) and triglyceride (p = 0.002, r = 0.55). CONCLUSION: FABP4 correlates with high DBP in the non-active and high triglyceride serum in the active episode.

The Potency of Moringa oleifera Lam. as Protective Agent in Cardiac Damage and Vascular Dysfunction.

Cardiac damage and vascular dysfunction due to underlying diseases, such as hypertension and cardiac thrombosis, or side effects from certain drugs may lead to critical illness conditions and even death. The phytochemical compounds in natural products are being prospected to protect the heart and vascular system from further damage. Moringa genus is a subtropical tree native to Asia and Africa, which includes 13 species; Moringa oleifera Lam. (MO) is the most cultivated for its beneficial uses. MO is also known as the "miracle tree" because it has been used traditionally as a food source and medicine to treat various diseases such as anemia, diabetes, and infectious or cardiovascular diseases. The phytochemical compounds identified in MO with functional activities associated with cardiovascular diseases are N,α-L-rhamnopyranosyl vincosamide, isoquercetin, quercetin, quercetrin, and isothiocyanate. This study aims to investigate the potency of the phytochemical compounds in MO as a protective agent to cardiac damage and vascular dysfunction in the cardiovascular disease model. This is a scoping review by studying publications from the reputed database that assessed the functional activities of MO, which contribute to the improvement of cardiac and vascular dysfunctions. Studies show that the phytochemical compounds, for example, N,α-L-rhamnopyranosyl vincosamide and quercetin, have the molecular function of antioxidant, anti-inflammation, and anti-apoptosis. These lead to improving cardiac contractility and protecting cardiac structural integrity from damage. These compounds also act as natural vasorelaxants and endothelium protective agents. Most of the studies were conducted on in vivo studies; therefore, further studies should be applied in a clinical setting.

Effect of cogon grass root ethanol extract on fatty acid binding protein 4 and oxidative stress markers in a sepsis mouse model.

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress-related factors in a sepsis mouse model. Methods: Twenty-nine male mice ( Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 µL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 µL/kg BW LPS for 14 d. Blood, liver, lymph, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant (Glutathione peroxidase 3 (GPx3) and superoxide dismutase), FABP4 levels, and immune system-associated biomarker levels (TNF-α, IL-6 and IL-1ß) were measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), and monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. Gpx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: ECGR reduces FABP4 level and modulating oxidative stress markers in sepsis mouse model.

CD36 is indispensable for nutrient homeostasis and endurance exercise capacity during prolonged fasting.

During fasting, most tissues including skeletal muscle heavily rely on utilization of fatty acids (FA) and minimize glucose use. In contrast, skeletal muscle prefers carbohydrate use as exercise intensity increases. In mice deficient for CD36 (CD36-/- mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in skeletal muscle even during fasting. In this study, we questioned how exercise endurance is affected during prolonged fasting in CD36-/- mice where glucose utilization is constantly increased. With or without a 24-h fast, a single bout of treadmill exercise was started at the speed of 10 m/min, and the speed was progressively increased up to 30 m/min until mice were exhausted. Running distance of wild type (WT) and CD36-/- mice was comparable in the fed state whereas that of CD36-/- mice was significantly reduced after a 24-h fast. Glycogen levels in liver and skeletal muscle were depleted both in WT and CD36-/- mice after a 24-h fast. In CD36-/- mice, FA uptake by skeletal muscle continued to be reduced during fasting. Glucose utilization also continued to be enhanced in the heart and oxidative skeletal muscle and glucose supply relative to its demand was diminished, resulting in accelerated hypoglycemia. Consequently, available energy substrates from serum and in muscle for exercise performance were very limited in CD36-/- mice during prolonged fasting, which could cause a remarkable reduction in exercise endurance. In conclusion, our study underscores the importance of CD36 for nutrient homeostasis to maintain exercise performance of skeletal muscle when nutrient supply is limited.

Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells.

The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0.423). These results suggest that 50 nM sodium selenite supplementation administered for 72 h prior to irradiation may protect CHEK-1 cells from irradiation-induced damage by inhibiting irradiation-induced apoptosis. Therefore, sodium selenite is a potential radioprotective compound for non-cancerous cells in clinical radiotherapy.

CD36 is indispensable for thermogenesis under conditions of fasting and cold stress.

Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36(-/-) mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36(-/-) mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue (125)I-BMIPP and the glucose analogue (18)F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36(-/-) mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36(-/-) mice after cold exposure. These findings strongly suggest that CD36(-/-) mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation.

Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice), as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT) and glycogen in skeletal muscle (SkM) was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs) are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.