Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.

Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis

SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion.

The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI:http://dx.doi.org/10.7554/eLife.00444.001

The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling and metabolic control

ABSTRACT Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWI/SNF chromatin-remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological signals. The ATP-dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different metabolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions

Discriminative and quantitative color-coding analysis of fluoroquinolones with dual-emitting lanthanide metal-organic frameworks

Color-coding analysis from chemicals of concern is in great demand, but faces low sensitivity and specificity, low resolution, and complex processing among the many challenges. Here, this work resolves these issues to enable the elusive quantitative detection of a variety of fluoroquinolone (FQ) antibiotics. A fluorescent sensor based on the dual-emitting lanthanide metal-organic frameworks combining Tb3+ and Eu3+ as the luminescent center and 1,3,5-benzenetricarboxylic acid as the ligand is constructed. Due to the different sensitization effects to lanthanide metals and different inherent fluorescence emissions of FQs, the sensor exhibits characteristic color variations towards nine FQ and enables the discriminative detection of multiple antibiotics with self-calibrated signals. For the first time, a polynomial surface fitting process is developed to correlate the coordinates of color-coding map and target concentration for quantitative analysis. Moreover, a smartphone-enabled sensing system is demonstrated for on-site imaging analysis of antibiotics. The demonstrated innovative antibiotic detection and color-coding-based signal processing approach will inform the development of cutting-edge analysis systems for public health and environmental monitoring.</p

Comparative Study on Milk Oligosaccharides in Buffalo and Cow Colostrum Milk

Milk oligosaccharides, which are free oligosaccharides in the mammalian milk, is one of the main composition in milk. Recent studies suggested that milk oligosaccharides improved immune function, and showed prebiotics as well as anti-infection actives. Milk oligosaccharides is also important for the intestinal development, neural development of infants. Buffalo (Bubalus bubalis) milk is the second important milk source besides cow milk It was also well accepted that buffalo milk was rich in nutritional content and was a high quality dairy product with good taste. However, researches on buffalo milk oligosaccharides was limited and only worked on American buffalo. On the other hand, milk oligosaccharides on Chinese buffalo is lacking. In the present study, colostrum milk samples from Guangxi buffalo were purified with solid phase extraction and modified by Aniline (Bn) derivative reagent. The sample was further purified by UPLC-ESI-Q-TOF-MS. The oligosaccharide components in buffalo colostrum were determined and compared with the cow colostrum milk. 19 kinds of oligosaccharides were found in cow colostrum and 9 in buffalo colostrum. Moreover, in both two kinds of colostrum, neutral disaccharide m/z 385.15, neutral trisaccharide m/z 547.21 and acidic oligosaccharide m/z 635.23 were the main composition. In general, the proportion of neutral oligosaccharides in buffalo milk was higher than that in cow milk, with a ratio of 88.88% and 63.16%, respectively.</p

A Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis

Dietary nutrients interact with gene networks to orchestrate adaptive responses during metabolic stress. Here, we identify Baf60a as a diet-sensitive subunit of the SWI/SNF chromatin-remodeling complexes in the mouse liver that links the consumption of fat- and cholesterol-rich diet to elevated plasma cholesterol levels. Baf60a expression was elevated in the liver following feeding with a western diet. Hepatocyte-specific inactivation of Baf60a reduced bile acid production and cholesterol absorption, and attenuated diet-induced hypercholesterolemia and atherosclerosis in mice. Baf60a stimulates expression of genes involved in bile acid synthesis, modification, and transport through a CAR/Baf60a feedforward regulatory loop. Baf60a is required for the recruitment of the SWI/SNF chromatin-remodeling complexes to facilitate an activating epigenetic switch on target genes. These studies elucidate a regulatory pathway that mediates the hyperlipidemic and atherogenic effects of western diet consumption

A Multicenter Randomized Controlled Pilot Trial Testing the Efficacy and Safety of Pterygopalatine Fossa Puncture Using One Acupuncture Needle for Moderate-to-Severe Persistent Allergic Rhinitis

Objective. To compare the efficacy and safety of pterygopalatine fossa puncture using one acupuncture needle inserted through the temporal fossa (intervention) and Chinese verum acupuncture (VA) in patients with moderate-to-severe persistent allergic rhinitis. Methods. The patients were randomized to an intervention group receiving pterygopalatine fossa puncture with one acupuncture needle for 4 weeks (once or twice weekly, 4–8 sessions in total, with a second course performed if required) or to a control group receiving individualized VA for 4 weeks (twice weekly, eight sessions in total). Patients were followed up 4 weeks later. Results. Ninety-six participants were assigned to intervention (n = 48) or VA (n = 48) groups. After treatment, differences in the total nasal symptom score (2004 Chinese version), total nonnasal symptom score, Rhinoconjunctivitis Quality of Life Questionnaire score, and symptomatic days were not significant between the groups (P>0.05 in all cases). Compared with the VA, the time to onset of effect in the intervention group was shorter and the duration of effectiveness was longer. The mean clinical waiting time was significantly shorter in the intervention group than in the control group (6.640 ± 3.035 min and 31.19 ± 10.216 min, respectively). The total number of sessions in the VA group was 384; 7 episodes of subcutaneous bleeding occurred but did not require treatment. The total number of sessions in the intervention group was 185. Two cases of subcutaneous bleeding (one of local hematoma during the intervention and the other one of bruising in the palpebra inferior on the day after intervention) resolved upon withdrawal from the study. Conclusions. Pterygopalatine fossa puncture using one acupuncture needle resulted in a shorter time to onset of effect, a longer duration of effectiveness, and less clinical waiting time when compared with VA. Though the significant differences for TNSS and TNNSS were shown within intervention and VA groups, there were no differences between the two groups. Although the rate of subcutaneous bleeding was low, these adverse events may influence patient compliance. This trial is registered with ISRCTN21980724