The prevalence of maternal obesity is increasing at an alarming rate, with maternal insufficient circulating adiponectin being identified as a crucial link to offspring metabolic disorders. Nutritional interventions during pregnancy have shown promise in mitigating the negative impacts of maternal obesity on offspring health. It is recommended that pregnant women with chronic metabolic diseases increase their consumption of whole grains such as brown rice. However, the specific mechanism through which brown rice consumption by obese pregnant women improves metabolic homeostasis in their offspring remains unclear. Here, we investigated the effects of a brown rice diet during pregnancy on the metabolic homeostasis of offspring exposed to maternal obesity. We found that the systemic energy metabolism homeostasis and the risk of obesity induced by high-fat diet (HFD) in the offspring of obese mothers were altered by the maternal brown rice diet during pregnancy, including reducing systemic and hepatic lipid levels, improving insulin resistance, and protecting hepatic steatosis. Mechanistically, the maternal brown rice diet induced DNA methylation reprogramming in the livers of offspring mice, resulting in enhanced demethylation of the adiponectin receptor AdipoR2 and increased transcription of AdipoR2 mRNA. Adiponectin binding to AdipoR2, regulated hepatic lipid metabolism through AMPKα and PPARα-mediated pathways, effectively ameliorating metabolic disorders in offspring of obese mothers. Our study provides novel insights into combating obesity risk and lays the groundwork for further exploration of the physiological benefits of whole grain brown rice.

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3.

Acylcarnitine (ACar) is a novel fuel source for activating thermogenesis in brown adipose tissue (BAT). However, whether ACar metabolism underlies BAT thermogenesis decline with aging remain unclear. Here, the L-carnitine-treated young and aging mice were used to investigate the effects of activation of ACar metabolism on BAT thermogenesis during aging. We showed that long term L-carnitine feeding, which results in an elevation in circulating ACar levels, failed to improve cold sensitivity of aging mice, which still displayed impaired thermogenesis and ACar metabolism in interscapular BAT (iBAT). The RNA-sequencing was used to identify the key regulator for the response of aging mice to LCar induced activation of ACar metabolism in BAT, and we identified Sirt3 as a key regulator for the response of aging mice to L-carnitine induced activation of ACar metabolism in iBAT. Then the adipose-specific Sirt3 knockout (Sirt3 AKO) mice were used to investigate the role of Sirt3 in ACar metabolism and thermogenesis of BAT and explore the underlying mechanism, and the results showed that Sirt3 AKO mice displayed defective ACar metabolism and thermogenesis in iBAT. Mechanically, Sirt3 regulated ACar metabolism via HIF1α-PPARα signaling pathway to promote iBAT thermogenesis, and knockdown or inhibition of HIF1α ameliorated impaired ACar metabolism and thermogenesis of iBAT in the absence of Sirt3. Collectively, we propose that Sirt3 regulated ACar metabolism is critical in maintaining thermogenesis in BAT of aging mice, which can promote the development of anti-aging intervention strategy.

ScopeBrown rice, the most consumed food worldwide, has been shown to possess beneficial effects on the prevention of metabolic diseases. However, the way in which maternal brown rice diet improves metabolism in offspring and the regulatory mechanisms remains unclear. The study explores the epigenetic regulation of offspring energy metabolic homeostasis by maternal brown rice diet during pregnancy.Methods and resultsFemale mice are fed brown rice during pregnancy, and then body phenotypes, the histopathological analysis, and adipose tissues biochemistry assay of offspring mice are detected. It is found that maternal brown rice diet significantly reduces body weight and fat mass, increases energy expenditure and heat production in offspring. Maternal brown rice diet increases uncoupling protein 1 (UCP1) protein level and upregulates the mRNA expression of thermogenic genes in adipose tissues. Mechanistically, protein kinase A (PKA) signaling is likely responsible in the induced thermogenic program in offspring adipocytes, and the progeny adipocytes browning program is altered due to decreased level of DNA methyltransferase 1 protein and hypomethylation of the transcriptional coregulator positive regulatory domain containing 16 (PRDM16).ConclusionsThese findings demonstrate that maternal brown rice during pregnancy improves offspring mice metabolic homeostasis via promoting adipose browning, and its mechanisms may be mediated by DNA methylation reprogramming.

SCORE:This study identifies the coding gene (aldB) of acetolactate decarboxylase (ALDC) as an important regulatory gene of the intracellular pH in Lactobacillus reuteri (L. reuteri), uncovering the important role of ALDC in regulating intracellular pH, morphological features, and antagonism properties in the probiotic organism L. reuteri. METHODS AND RESULTS:The aldB mutant (ΔaldB) of L. reuteri is established using the homologous recombination method. Compare to the wild-type (WT) strain, the ΔaldB strain shows a smaller body size, grows more slowly, and contains more acid in the cell cytoplasm. The survival rate of the ΔaldB strain is much lower in low pH and simulated gastric fluid (SGF) than that of the WT strain, but higher in simulated intestinal fluid (SIF). The antagonism test demonstrates the ΔaldB strain can inhibit Listeria monocytogenes (L. monocytogenes) and Salmonella more effectively than the WT strain. Additionally, there is a dramatic decrease in the adhesion rate of Salmonella to Caco-2 and HT-29 cells in the presence of the ΔaldB strain compared to the WT strain. Simultaneously analyze, the auto-aggregation, co-aggregation, cell surface hydrophobicity (CSH), hemolytic, temperature, NaCl, oxidative stress, and antibiotic susceptibility of the ΔaldB strain are consistent with the features of probiotics. CONCLUSION:This study highlights that the aldB gene plays a significant role in the growth and antibacterial properties of L. reuteri.

5-Heptadecylresorcinol (AR-C17), a primary biomarker of whole grain (WG) consumption, has been demonstrated to improve the thermogenic activity of aging mice. However, the intricate regulatory mechanism is not fully understood. This study conducted metabolomics analysis on young and aging mice with or without AR-C17 administration after cold exposure. The results showed that the aging mice displayed lower levels of acylcarnitine (ACar) in their plasma compared with the young mice during cold exposure, and 150 mg/kg/day of AR-C17 administration for 8 weeks could increase the plasma ACar levels of aging mice. ACar has been reported to be an essential metabolic fuel for the thermogenesis of brown adipose tissue (BAT). AR-C17 had similar effects on the ACar levels in the BAT as on the plasma of the aging mice during cold exposure. Furthermore, the aging mice had reduced ACar metabolism in the BAT, and AR-C17 could improve the ACar metabolism in the BAT of aging mice, thereby promoting the metabolic utilization of ACar by BAT. Moreover, the glucose and lipid levels of aging mice could be improved by AR-C17. This study revealed a deeper metabolic mechanism involved in the AR-C17-mediated thermogenic regulation of BAT, providing a new theoretical basis for the nutrition and health benefits of WG.

5-Heptadecylresorcinol (AR-C17), a well-known biomarker for whole grain rye consumption, is a primary homolog of alkylresorcinols. In this study, the effects of AR-C17 on the thermogenesis of brown adipocytes and 3T3-L1 adipocytes were investigated. The results showed that AR-C17 increased sirtuin 3 (Sirt3) expression, and the expressions of specific thermogenic genes in adipocytes were increased. Furthermore, AR-C17 increased the mitochondrial functions during the thermogenic activation of adipocytes. In in vivo study, AR-C17 increased the cold tolerance and thermogenic capacity of adipose tissues in aging mice. In addition, Sirt3 activity was required for AR-C17-induced thermogenesis. Meanwhile, AR-C17 increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and AMPK was involved in the regulation of AR-C17 on thermogenic adipocytes. Mechanically, AR-C17 upregulated a Sirt3-AMPK positive-feedback loop in adipocytes and further increased the expression of uncoupling protein 1 to activate thermogenesis. This study indicated that AR-C17 could be a promising thermogenic activator of adipocytes to alleviate obesity and aging-associated metabolic diseases.

Abstract Background Hypercholesterolemia is closely associated with an increased risk of cardiovascular diseases. l-Arabinose exhibited hypocholesterolemia properties, but underlying mechanisms have not been sufficiently investigated. This study aimed to elucidate the mechanisms of l-arabinose on hypocholesterolemia involving the enterohepatic circulation of bile acids. Methods Thirty six-week-old male mice were randomly divided into three groups: the control group and the high-fat-high-sucrose diet (HFHSD)-fed group were gavaged with distilled water, and the l-arabinose-treated group were fed HFHSD and received 400 mg/kg/day l-arabinose for 12 weeks. Serum and liver biochemical parameters, serum and fecal bile acid, cholesterol and bile acid metabolism-related gene and protein expressions in the liver and small intestine were analyzed. Results l-Arabinose supplementation significantly reduced body weight gain, lowered circulating low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C) levels, and efficiently alleviated hepatic inflammation and lipid accumulations in HFHSD-fed mice. l-Arabinose inhibited cholesterol synthesis via downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Additionally, l-arabinose might facilitate reverse cholesterol transport, evidenced by the increased mRNA expressions of low-density lipoprotein receptor (LDL-R) and scavenger receptor class B type 1 (SR-B1). Furthermore, l-arabinose modulated ileal reabsorption of bile acids mainly through downregulation of ileal bile acid-binding protein (I-BABP) and apical sodium-dependent bile acid transporter (ASBT), resulting in the promotion of hepatic synthesis of bile acids via upregulation of cholesterol-7α-hydroxylase (CYP7A1). Conclusions l-Arabinose supplementation exhibits hypocholesterolemic effects in HFHSD-fed mice primarily due to regulation of bile acid metabolism-related pathways.

SCOPE:Highland barley tea is a kind of caffeine-free cereal tea. Previous studies have shown that it is rich in polyphenol flavonoids. Here, the effect of Highland barley tea polyphenols (HBP) on the production of advanced glycosylation end-products and alleviate the skeletal muscle damage is systematically investigated.METHODS AND RESULTS:HBP effectively inhibits the formation of AGEs in vitro, and 12 phenolic compounds are identified. In addition, d-galactose is used to construct a mouse senescence model and intervenes with different doses of HBP. It is found that high doses of HBP effectively inhibit AGEs in serum and flounder muscle species and increased muscle mass in flounder muscle; also, high doses of HBP increase the expression of the mitochondrial functional protein SIRT3 and decrease the expression of myasthenia-related proteins. Furthermore, cellular experiments show that AGEs can significantly increase oxidative stress in skeletal muscle.CONCLUSION:These data indicate that the relationship between the biological activity and HBP properties is relevant since Highland barley can be a potential functional food to prevent AGEs-mediated skeletal muscle damage.

Hydroxysafflor yellow A (HSYA) is the main bioactive component of safflower and has been reported to have significant health-promoting abilities. However, the regulation of HSYA on different types of skeletal myofibers is largely unknown. Here, in vitro experiments found that the water extract of safflower could significantly increase MyHC I, MB and Tnni1 mRNA expression while downregulating MyHC IIb mRNA expression. Furthermore, HSYA triggered fast-to-slow fiber-type switching and increased gene expression related to mitochondrial biosynthesis both in vitro and in vivo. Autodock analyses proved that FoxO1 is a potential target of HSYA, and qRT-PCR and western blotting further showed that HSYA significantly promoted the activation of the FoxO1 signaling pathway. Additionally, the levels of PGC1α, downstream of FoxO1, also significantly increased after HSYA treatment. Together, our findings suggested that HSYA triggered a fast-to-slow myofiber-type shift through the FoxO1 signaling pathway.

Rice bran is rich in nutrients and bioactive components, which plays an important role in reducing dyslipidemia and regulating intestinal flora. However, due to the rice bran's instability resulting from rancidity during storage, the development is limited. E-nose, GC-MS and E-tongue were used to monitor the flavor and bitterness of different stabilized rice bran during accelerated storage, and the change of physicochemical properties in rice bran was determined. The rice bran flavor significantly changed after five stabilization treatments. The bitterness increased during storage, but the growth was small (from 7.39 to 7.62). Besides, after stabilization treatments, lipase (LA) activities gradually decreased from 10.11 to 2.03 mg/g, and lipoxygenase (Lox) activities decreased from 3.71 to 1.38 U/g. These results comprehensively elucidate changes in volatile composition, bitterness and physicochemical properties of stabilized rice bran samples during storage and lay the foundation for improving its acceptability and edibility in the future.

Gluten is widely used as a high-quality protein material in the food industry, however, low solubility restricts its development and applications. In this study, gluten was treated with lactate and sodium lactate for lactylation. Lactylation of gluten altered surface charges of the protein, leading to a significant improvement in the solubility. An improvement in oil absorption capacity (OAC) could be attributed to a decrease in protein folding degree after lactylation. In addition, the emulsifying properties of gluten were significantly enhanced. The introduction of lactate group also significantly increased the viscoelasticity of gluten. Fourier transform infrared spectroscopy (FTIR) showed there was a significant decrease in β-turns content and a significant increase in β-sheets content. The folded conformation of gluten was gradually extended after lactation by fluorescence spectroscopy measurement. Both in lactate and sodium lactate treatment, the maximum emission wavelength indicated a blue shift, and the UV intensity showed an increase. These results could demonstrate that lactylation could extend the structure and improve the functional property.

Objective: With the prevalence of diabetes worldwide, it is urgent to find a suitable treatment. Recently, the ketogenic diet has shown beneficial effects in reducing blood glucose, but some concerns have been raised about its probable side effects, such as hyperlipidemia and hepatic steatosis. Because a low-carbohydrate diet replaces part of the fat with carbohydrates on the basis of the ketogenic diet, we would like to know whether it does better in treating type 2 diabetes. The aim of this study was to explore the possibility of a low-carbohydrate diet as a substitute for a ketogenic diet intervention in mice with type 2 diabetes. Methods: C57 BL/6 J mice with type 2 diabetes, constructed by a high-fat diet combined with streptozotocin, were fed a standard diet, a high-fat diet, a low-carbohydrate diet, or a ketogenic diet for 14 wk, respectively. Then glucose and insulin tolerance tests were conducted. At the end of the study, blood and liver samples were collected and analyzed for serum biochemical indicators, histopathologic evaluation, hepatic lipid and glycogen content, and expression levels of mRNA and protein. Results: Reduced blood glucose could be observed in both low-carbohydrate and ketogenic diets, as well as improvement in glucose tolerance and insulin sensitivity. However, the ketogenic diet decreased liver glycogen content and promoted gluconeogenesis. Mechanistically, this effect was due to inhibition of phosphorylated AMP-activated protein kinase, which could be improved by a low-carbohydrate diet. Regarding lipid metabolism, the ketogenic diet increased lipid oxidation and reduced de novo lipogenesis, but the hepatic lipid content still inevitably increased. On the contrary, the low-carbohydrate diet reduced triacylglycerols and markers of liver damage. Conclusions: Collectively, these findings suggest that both diets are effective in lowering blood glucose, improving glucose tolerance, and raising insulin sensitivity. Moreover, the low-carbohydrate diet plays a role in inhibiting hepatic gluconeogenesis and improving lipid metabolism. The results suggest that the two diets have different effects on glucose and lipid metabolism, and that the low-carbohydrate diet might have more benefits in the treatment of type 2 diabetes mellitus. (C) 2021 Elsevier Inc. All rights reserved.

Bacillus subtilis , a plant-beneficial bacterial species exhibiting good biocontrol capabilities, has been widely used in agricultural production. The endophytic strain 9407 can efficiently control bacterial fruit blotch (BFB) caused by the gram-negative bacterium Acidovorax citrulli . However, the mechanism underlying its biocontrol ability remains poorly understood. Given the genomic diversity of B. subtilis , strain 9407 was sequenced and assembled in this study to determine the genome information associated with its biocontrol traits. A combination of core genome phylogenetic analysis and average nucleotide identity (ANI) analysis demonstrated that the 9407 strain belonged to B. subtilis . Various functional genes related to biocontrol traits, i.e., biofilm formation, motility, pathogen inhibition, plant growth promotion, and induction of systemic resistance, were identified in B. subtilis 9407. Four secondary metabolite biosynthesis gene clusters with antibacterial ability were also found in the B. subtilis 9407 genome, including newly identified subtilosin A, bacilysin, and bacillaene, and the previously reported surfactin. Mutants lacking sboA or bacG , which are defective in synthesizing subtilosin A or bacilysin, showed decreased inhibitory activity against A. citrulli MH21, and the triple mutant with deleted sboA , bacG, and srfAB almost completely lost its inhibitory activity. The biofilm formation and swarming motility of the sboA and bacG mutants also decreased, in turn leading to decreased colonization on melon roots and leaves. Under greenhouse conditions, the biocontrol efficacy of the sboA and bacG mutants against BFB on melon leaves decreased by 21.4 and 32.3%, respectively. Here, we report a new biocontrol pathway of B. subtilis 9407 against BFB, in which subtilosin A and bacilysin contributed to the biocontrol efficacy by improving antibacterial activity and colonization ability of the strain. The comprehensive genomic analysis of B. subtilis 9407 improves our understanding of the biocontrol mechanisms of B. subtilis , providing support for further research of its biocontrol mechanisms and field applications.

Ulcerative colitis (UC) is one of the most prevalent inflammatory bowel diseases (IBD) worldwide, while oat β-glucan has been shown to suppress the progress of colitis in UC mice. However, the underlying mechanism of oat β-glucan in ameliorating colitis is unclear and the role of gut microbiota in the protective effect of oat β-glucan against colitis remains unknown. In the present study, we aim to investigate the effect of oat β-glucan on gut microbiota in colitis mice and explore the health effect related mechanism. Dextran sulfate sodium (DSS) was used to induce the colitis model in mice. The results showed that β-glucan treatment attenuated hematochezia, splenomegaly and colon shortening in colitis mice. Histological evaluation of H&E and TUNEL staining showed that β-glucan treatment suppressed DSS-induced colonic inflammatory infiltration and reduced cell apoptosis levels of colon tissues. mRNA expression levels of the pro-inflammatory factors were also significantly reduced in the β-glucan group. Moreover, β-glucan treatment increased the protein and mRNA expression levels of tight junction proteins. Analysis of gut microbiota community showed that β-glucan treatment modulated gut microbial composition and structure at the OTU level in colitis mice. Further analysis of gut microbial metabolism revealed that β-glucan treatment significantly increased acetate, propionate and butyrate concentrations, and affected microbial metabolome in colitis mice. Notably, the increased acetate and propionate concentrations could directly affect pro-inflammatory factor expression levels and tight junction protein levels. In contrast, the changes in metabolic profiles affected pro-inflammatory factor levels and thus affected tight junction protein levels. Overall, our study revealed that oat β-glucan ameliorated DSS-induced colitis in mice simultaneously through regulating gut-derived short-chain fatty acids (SCFAs) and microbial metabolic biomarkers. Our study demonstrated that oat β-glucan could be an effective nutritional intervention strategy towards targeting gut microbiota metabolism for ameliorating colitis.