The Role of Neuropeptide Y in Adipocyte-Macrophage Crosstalk during High Fat Diet-Induced Adipose Inflammation and Liver Steatosis

Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY−/− mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD

Calorie restriction minimizes activation of insulin signaling in response to glucose: Potential involvement of the growth hormone-insulin-like growth factor 1 axis

Calorie restriction (CR) may modulate insulin signaling in response to energy intake through suppression of the growth hormone (GH)-IGF-1 axis. We investigated the glucose-stimulated serum insulin response and subsequent alterations in insulin receptor (IR), Akt, and FoxO1 in the rat liver and quadriceps femoris muscle (QFM). Nine-month-old wild-type (W) male Wistar rats fed ad libitum (AL) or a 30% CR diet initiated at 6 weeks of age and GH-suppressed transgenic (Tg) rats fed AL were killed 15 min after intraperitoneal injection of glucose or saline. In W-AL rats, the serum insulin concentration was elevated by glucose injection. Concomitantly, the phosphorylated (p)-IR and p-Akt levels were increased in both tissues. The active FoxO1 level was decreased in the liver, but not significantly in the QFM. In W-CR and Tg-AL rats, the serum insulin response was lower, and no significant changes were noted for the p-IR, p-Akt, or active FoxO1 levels in the liver. In the QFM, the p-Akt level was increased in W-CR and Tg-AL rats with an insignificant elevation of p-IR levels. The phenotypic similarity of W-CR and Tg-AL rats suggest that CR minimizes activation of insulin signaling in response to energy intake mostly through the GH-IGF-1 axis

Optimal Band Selection for Airborne Hyperspectral Imagery to Retrieve a Wide Range of Cyanobacterial Pigment Concentration Using a Data-Driven Approach

Understanding the concentration and distribution of cyanobacteria blooms is an important aspect of managing water quality problems and protecting aquatic ecosystems. Airborne hyperspectral imagery (HSI)-which has high temporal, spatial, and spectral resolutions-is widely used to remotely sense cyanobacteria bloom, and it provides the distribution of the bloom over a wide area. In this study, we determined the input spectral bands that were relevant in effectively estimating the main two pigments (PC, Phycocyanin; Chl-a, Chlorophyll-a) of cyanobacteria by applying data-driven algorithms to HSI and then evaluating the change in the spatio-temporal distribution of cyanobacteria. The input variables for the algorithms consisted of reflectance band ratios associated with the optical properties of PC and Chl-a, which were calculated by the selected hyperspectral bands using a feature selection method. The selected input variable was composed of six reflectance bands (465.7-589.6, 603.6-631.8, 641.2-655.35, 664.8-679.0, 698.0-712.3, and 731.4-784.1 nm). The artificial neural network showed the best results for the estimation of the two pigments with average coefficients of determination 0.80 and 0.74. This study proposes relevant input spectral information and an algorithm that can effectively detect the occurrence of cyanobacteria in the weir pool along the Geum river, South Korea. The algorithm is expected to help establish a preemptive response to the formation of cyanobacterial blooms, and to contribute to the preparation of suitable water quality management plans for freshwater environments

Application of airborne hyperspectral imagery to retrieve spatiotemporal CDOM distribution using machine learning in a reservoir

Colored dissolved organic matter (CDOM) in inland waters is used as a proxy to estimate dissolved organic carbon (DOC) and may be a key indicator of water quality and nutrient enrichment. CDOM is optically active fraction of DOC so that remote sensing techniques can remotely monitor CDOM with wide spatial coverage. However, to effectively retrieve CDOM using optical algorithms, it may be critical to select the absorption co-efficient at an appropriate wavelength as an output variable and to optimize input reflectance wavelengths. In this study, we constructed a CDOM retrieval model using airborne hyperspectral reflectance data and a machine learning model such as random forest. We evaluated the best combination of input wavelength bands and the CDOM absorption coefficient at various wavelengths. Seven sampling events for airborne hyperspectral imagery and CDOM absorption coefficient data from 350 nm to 440 nm over two years (2016-2017) were used, and the collected data helped train and validate the random forest model in a freshwater reservoir. An absorption co-efficient of 355 nm was selected to best represent the CDOM concentration. The random forest exhibited the best performance for CDOM estimation with an R2 of 0.85, Nash-Sutcliffe efficiency of 0.77, and percent bias of 3.88, by using a combination of three reflectance bands: 475, 497, and 660 nm. The results show that our model can be utilized to construct a CDOM retrieving algorithm and evaluate its spatiotemporal variation across a reservoir

A key role for neuropeptide Y in lifespan extension and cancer suppression via dietary restriction

Knowledge of genes essential for the life-extending effect of dietary restriction (DR) in mammals is incomplete. In this study, we found that neuropeptide Y (Npy), which mediates physiological adaptations to energy deficits, is an essential link between DR and longevity in mice. The lifespan-prolonging effect of lifelong 30% DR was attenuated in Npy-null mice, as was the effect on the occurrence of spontaneous tumors and oxidative stress responses in comparison to wild-type mice. In contrast, the physiological processes activated during adaptation to DR, including inhibition of anabolic signaling molecules (insulin and insulin-like growth factor-1), modulation of adipokine and corticosterone levels, and preferential fatty acid oxidation, were unaffected by the absence of Npy. These results suggest a key role for Npy in mediating the effects of DR. We also provide evidence that most of the physiological adaptations to DR could be achieved in mice without Npy

Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect

Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12. weeks of age. Adipoq-RD and -HFD mice at 6. months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR

Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic

Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1 +/- mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a-/- mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/- mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring