Inflammation promotes synucleinopathy propagation.

The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.

Limonium tetragonum Promotes Running Endurance in Mice through Mitochondrial Biogenesis and Oxidative Fiber Formation.

The purpose of this study was to examine whether Limonium tetragonum, cultivated in a smart-farming system with LED lamps, could increase exercise capacity in mice. C57BL/6 male mice were orally administered vehicle or Limonium tetragonum water extract (LTE), either 30 or 100 mg/kg, and were subjected to moderate intensity treadmill exercise for 4 weeks. Running distance markedly increased in the LTE group (100 mg/kg) by 80 ± 4% compared to the vehicle group, which was accompanied by a higher proportion of oxidative fibers (6 ± 6% vs. 10 ± 4%). Mitochondrial DNA content and gene expressions related to mitochondrial biogenesis were significantly increased in LTE-supplemented gastrocnemius muscles. At the molecular level, the expression of PGC-1α, a master regulator of fast-to-slow fiber-type transition, was increased downstream of the PKA/CREB signaling pathway. LTE induction of the PKA/CREB signaling pathway was also observed in C2C12 cells, which was effectively suppressed by PKA inhibitors H89 and Rp-cAMP. Altogether, these findings indicate that LTE treatment enhanced endurance exercise capacity via an improvement in mitochondrial biosynthesis and the increases in the formation of oxidative slow-twitch fibers. Future study is warranted to validate the exercise-enhancing effect of LTE in the human.

Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression.

Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans, and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance.

Association of Polygenetic Risk Scores Related to Immunity and Inflammation with Hyperthyroidism Risk and Interactions between the Polygenetic Scores and Dietary Factors in a Large Cohort.

Graves's disease and thyroiditis induce hyperthyroidism, the causes of which remain unclear, although they are involved with genetic and environmental factors. We aimed to evaluate polygenetic variants for hyperthyroidism risk and their interaction with metabolic parameters and nutritional intakes in an urban hospital-based cohort. A genome-wide association study (GWAS) of participants with (cases; n = 842) and without (controls, n = 38,799) hyperthyroidism was used to identify and select genetic variants. In clinical and lifestyle interaction with PRS, 312 participants cured of hyperthyroidism were excluded. Single nucleotide polymorphisms (SNPs) associated with gene-gene interactions were selected by hyperthyroidism generalized multifactor dimensionality reduction. Polygenic risk scores (PRSs) were generated by summing the numbers of selected SNP risk alleles. The best gene-gene interaction model included tumor-necrosis factor (TNF)_rs1800610, mucin 22 (MUC22)_rs1304322089, tribbles pseudokinase 2 (TRIB2)_rs1881145, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)_rs231775, lipoma-preferred partner (LPP)_rs6780858, and human leukocyte antigen (HLA)-J_ rs767861647. The PRS of the best model was positively associated with hyperthyroidism risk by 1.939-fold (1.317-2.854) after adjusting for covariates. PRSs interacted with age, metabolic syndrome, and dietary inflammatory index (DII), while hyperthyroidism risk interacted with energy, calcium, seaweed, milk, and coffee intake (P < 0.05). The PRS impact on hyperthyroidism risk was observed in younger (<55 years) participants and adults without metabolic syndrome. PRSs were positively associated with hyperthyroidism risk in participants with low dietary intakes of energy (OR = 2.74), calcium (OR = 2.84), seaweed (OR = 3.43), milk (OR = 2.91), coffee (OR = 2.44), and DII (OR = 3.45). In conclusion, adults with high PRS involved in inflammation and immunity had a high hyperthyroidism risk exacerbated under low intakes of energy, calcium, seaweed, milk, or coffee. These results can be applied to personalized nutrition in a clinical setting.

Draft genome of the Korean smelt Hypomesus nipponensis and its transcriptomic responses to heat stress in the liver and muscle.

Pond smelt (Hypomesus nipponensis) is a cold-freshwater fish species and a winter economic aquaculture resource in South Korea. Because of its high susceptibility to abnormal water temperature from global warming, a large number of smelt die in hot summers. Here, we present the first draft genome of H. nipponensis and transcriptomic changes in molecular mechanisms or intracellular responses under heat stress. We combined Illumina and PacBio sequencing technologies to generate the draft genome of H. nipponensis. Based on the reference genome, we conducted transcriptome analysis of liver and muscle tissues under normal (NT, 5°C) vs. warm (HT, 23°C) conditions to identify heat stress-induced genes and gene categories. We observed a total of 1987 contigs with N50 of 0.46 Mbp, with the largest contig (3.03 Mbp) in the assembled genome. A total of 20,644 protein-coding genes were predicted, and 19,224 genes were functionally annotated: 15,955 genes for Gene Ontology terms and 11,560 genes for KEGG Orthology. We conducted the lost and gained genes analysis compared with three species that: human, zebrafish, and salmon. In the lost genes analysis, we detected that smelt lost 4461 (22.16%), 2825 (10.62%), and 1499 (3.09%) genes compare with above three species, respectively. In the gained genes analysis, we observed that smelt gained 1133 (5.49%), 1670 (8.09%), and 229 (1.11%) genes compared with the above species, respectively. From transcriptome analysis, a total of 297 and 331 differentially expressed genes (DEGs) with a false discovery rate <0.05 were identified in the liver and muscle tissues, respectively. Gene enrichment analysis of DEGs indicates that upregulated genes were significantly enriched for lipid biosynthetic process (GO:0008610, P < 0.001) and regulation of apoptotic process (GO:0042981, P < 0.01), and genes were downregulated by immune responses such as myeloid cell differentiation (GO:0030099, P < 0.001) in the liver under heat stress. In muscle tissue, upregulated genes were enriched for hypoxia (GO:0001666, P < 0.05), transcription regulator activity (GO:0140110, P < 0.001), and calcium-release channel activity (GO:0015278, P < 0.01), and genes were downregulated for a nicotinamide nucleotide biosynthetic process (GO:0019359, P < 0.01). The results of KEGG pathway analysis were similar to that of gene enrichment analysis. The draft genome and transcriptomic of H. nipponensis will be a useful genetic resource for functional and evolutionary studies. Our findings will improve understanding of molecular mechanisms and heat responses and be useful for predicting survival of the smelt and its closely related species under global warming.

ZW800-PEG: A Renal Clearable Zwitterionic Near-Infrared Fluorophore for Potential Clinical Translation.

Near-infrared (NIR) fluorescence imaging has advanced medical imaging and image-guided interventions during the past three decades. Despite tremendous advances in imaging devices, surprisingly only a few dyes are currently available in the clinic. Previous fluorophores, ZW800-1A and ZW800-1C, significantly improved the poor performance of the FDA-approved indocyanine green. However, ZW800-1A is not stable in serum and ZW800-1C induces severe stacking in aqueous media. To solve such dilemmas, ZW800-PEG was designed by introducing a flexible yet stable thiol PEG linker. ZW800-PEG shows high solubility in both aqueous and organic solvents, thus improving renal clearance with minimal binding to serum proteins during systemic circulation. The sulfide group on the meso position of the heptamethine core improves serum stability and physicochemical properties including the maximum emission wavelength shift to 800 nm, enabling the use of ZW800-PEG for image-guided interventions and augmenting photothermal therapy.

The complete mitochondrial genome of Tachysurus nitidus (Siluriformes: Bagridae) from the Geum river in Korea.

The complete mitochondrial genome of a bagrid catfish, Tachysurus nitidus was completely analyzed by the primer walking method. It was composed of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region with a total length of 16,537 bp. In the phylogenetic tree, using mitochondrial genome of 13 related sequences revealed that T. nitidus (MW451217) of Korea is clustered with T. nitidus (KC822643) of China. This complete mitochondrial genome provides an important resource for reviewing the phylogenetic relationships and taxonomic status of the bagrid species.

Associations between metabolic syndrome and urinary Na-to-K ratio and glomerular filtration rate in middle-aged adults regardless of Na and K intakes.

BACKGROUND: Intake of Na-to-K ratio (I-Na/K), urinary Na-to-K ratio (U-Na/K), and estimated glomerular filtration rate (GFR) have been reported to be risk factors of metabolic syndrome (MetS), but results are inconsistent. We examined the hypothesis that U-Na/K, GFR, and a preference for salty foods are associated with MetS risk and the hypothesis in 8540 adults aged over 40 years without chronic kidney disease. METHODS: Participants were categorized using a U-Na/K of < 2.1 (low-U-Na/k) and a GFR of < 60 mL/min (low-GFR). A GFR of 60-90 mL/min was considered as a normal level, since it is a normal or marginal disease state. Correlations and associations were determined using Pearson's correlation coefficients and logistic regression analysis after adjusting for covariates related to MetS. RESULTS: U-Na/K, but not I-Na/K, was positively correlated with blood pressure (r2 = 0.20, P < 0.0001). The GFR was negatively correlated with age, gender, HOMA-B, and MetS (r2 = - 0.14 to - 0.595, P < 0.0001), and positively correlated with education, current smoking, and alcohol intake (r2 = 0.21 to 0.40, P < 0.0001). MetS risk had a positive association with the following combinations with low-U-Na/K + low-GFR, high-U-Na/K + high-GFR, and high-U-Na/K +low-GFR by 1.830-, 3.182-, and 3.696-fold, respectively, as compared with low-U-Na/K + high-GFR. Risks of the MetS components (abdominal obesity, hypertriglyceridemia, hypo-HDL-cholesterolemia, hypertension, and hyperglycemia) were similarly associated with U-Na/K and GFR, though hypertension had the strongest association. Hypertension risk had positive associations with low-U-Na/K + low-GFR, high-U-Na/K + high-GFR, and high-U-Na/K + low-GFR by 1.526-, 14.06-, and 7.079-fold, respectively, as compared with low-U-Na/K + high-GFR. CONCLUSION: MetS risk was found to be associated with U-Na/K and GFR regardless of I-Na/K. Women need to maintain a high GFR to reduce the MetS risk, especially the risk of hypertension.

Mental stress and physical activity interact with the genetic risk scores of the genetic variants related to sweetness preference in high sucrose-containing food and glucose tolerance.

We hypothesized that subjects with genetic variants that increase sweet taste preference would consume more sucrose-containing foods and have altered energy and glucose metabolisms, which would have interactions with lifestyles. Korean genome and epidemiology study (KoGES) was conducted to determine genetic variants and lifestyles including nutrient intakes by the Korean Center for Disease and Control during 2004-2013. Subjects were 8,842 adults aged 40-69 years in Ansan/Ansung cohorts in Korea. The associations between genetic risk scores(GRS) selected for influencing higher sweet preference and energy and glucose metabolism were examined using logistic regression after adjusting for covariates. GRS included 8 SNPs, TAS1R2_rs61761364, SLC2A5_rs11121306, SLC2A7_ rs769902, SLC2A5_rs765618, TRPM5_rs1965606, TRPV1_rs224495, TRPV1_ rs8065080, and TRPV1_rs8078502. Sweet taste preference was higher by 1.30-folds in high GRS than in low GRS (p < .0001). Consistent with sweet taste preference, carriers with high GRS had a higher intake of sucrose-containing foods by 1.25 (1.08-1.46)-fold than those with low GRS after adjusting age, gender, BMI, and energy intake. However, glucose intolerance risk was rather lower by 0.861 (0.76-0.98)-fold in high GRS than low GRS (p < .05). GRS tended to interact with mental stress to affect sucrose intake (p = .048). Only in low mental stress levels, sucrose-containing food intake was higher in high GRS than low GRS. There was an interaction of GRS with physical activity to influence glucose intolerance. Serum glucose concentrations were lower by 0.808-folds in high GRS than low GRS only in a high physical activity state. In conclusion, adults with genetically high sweet taste preference had a positive association with high sucrose-containing food intakes and improved glucose tolerance. The genetic impact on sweetness preference was associated with offset by high mental stress and lack of physical activity.

Gene-gene and gene-lifestyle interactions of AKAP11, KCNMA1, PUM1, SPTBN1, and EPDR1 on osteoporosis risk in middle-aged adults.

OBJECTIVES: Osteoporosis is associated with genetic and environmental factors. The aim of this article was to determine how the polygenic risk scores (PRS) of genetic variants that affect osteoporosis and its related signaling interact with the lifestyle of middle-aged adults. METHODS: The study examined 8845 participants from Ansan/Ansung cohorts. Osteoporosis was defined as a T-score of bone mineral density ≤-2.5 in either the wrist or tibia; 1136 participants had osteoporosis. Genome-wide association studies of individuals 40 to 65 y of age were conducted and the best gene-gene interactions from the genetic variants related to osteoporosis were selected and explored using the generalized multifactor dimensionality reduction method. PRS for the best model (PRSBM) was calculated by weighted PRS that was divided into low, medium, and high groups. RESULTS: The model that contributed the most influence on osteoporosis risk with gene-gene interactions included AKAP11_rs238340, KCNMA1_ rs628948, PUM1_rs7529390, SPTBN1_ rs6752877, and EPDR1_rs2722298. The risk for osteoporosis in the tibia was elevated by 1.71-fold in the high PRSBM group compared with the low PRSBM group. Energy and nutrient intake did not have any interaction with PRSBM and thus did not influence risk for osteoporosis. However, interestingly, only coffee and caffeine intake did interact with PRSBM and affected risk for osteoporosis. In patients with low coffee (<3 cup/wk) and caffeine(<60 mg/d) consumption, osteoporosis risk was higher in the high PRSBM group than the low PRSBM group by 2.27- and 2.29-fold, respectively. In the low coffee intake group, bone mineral density in the high PRSBM group was significantly higher than in the low PRSBM arm. CONCLUSIONS: Carriers with high PRSBM increased susceptibility to osteoporosis, especially in low coffee and caffeine intake. The results can be applied to personalized nutrition for lowering the risk for osteoporosis.

Carbohydrate and sodium intake and physical activity interact with genetic risk scores of four genetic variants mainly related to lipid metabolism to modulate metabolic syndrome risk in Korean middle-aged adults.

Metabolic syndrome (MetS) risk is influenced by genetic and environmental factors. The present study explored genetic risk scores (GRS) of genetic variants that influence the MetS and the effect of interactions between GRS and nutrient intake on MetS risk. The genetic variants that influence MetS risk were selected by genome-wide association study after adjusting for age, sex, area of residence and BMI in 8840 middle-aged adults. GRS were calculated by summing the risk alleles of the selected SNP and divided into low (0-1), medium (2-3) and high (4-7) risk groups, and the relationships between the MetS and GRS were determined by logistic regression after adjusting covariates involved in MetS risk. We also analysed the interaction between GRS and lifestyles. Four genetic variants (APOA5_rs651821, EFCAB4B_rs4766165, ZNF259_rs2160669 and APOBEC1_rs10845640) were selected because they increased MetS risk after adjusting for covariates. Individuals with medium-GRS and high-GRS alleles had a higher MetS risk by 1·48- and 2·23-fold, respectively, compared with those with low-GRS after adjusting for covariates. The increase in MetS risk was mainly related to serum TAG and HDL-cholesterol concentrations. The GRS had an interaction with carbohydrate (CHO) and Na intakes and daily physical activities for MetS risk. In conclusion, Asian middle-aged adults with high-GRS alleles were at increased MetS risk mainly due to dyslipidaemia. High daily physical activity (≥1 h moderate activity per d) reduced the MetS risk but a low-CHO diet (<65 % of total energy intake) increased the risk in carriers with high-GRS alleles. Low Na intake (<1·6 g Na intake/4 MJ) did not decrease its risk.

Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans.

Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Although sirtuin 6 (Sirt6) deficiency has previously been implicated in diet-induced obesity and systemic insulin resistance, the adipocyte-specific role of Sirt6 in the regulation of adipose tissue inflammation and systemic metabolic dysfunction in mice fed normal chow and in humans remains elusive. Here, using Adipoq-Cre-mediated adipocyte-specific Sirt6 knockout (aS6KO) mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild-type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in the adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of the canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue.

Total ionization cross section of cyclic organic molecules.

Two independent methods, namely, Binary-encounter Bethe (BEB) and complex scattering potential-ionization contribution (CSP-ic) methods, are employed to calculate the total ionization cross section (Qion) for cyclic organic molecules from ionization threshold to 5 keV for which there is a paucity of data in the literature. The Qion calculated with the (BEB/ωB97X) combination is found to give good agreement with the experimental results, the CSP-ic method, and the Qion calculated from Irikura orbital energies. The Qion for most of the targets are calculated for the first time over such a wide energy range. Hence, to check the consistency and reliability of the present data, we have also computed the static polarizability for all the targets and the variation of maximum ionization cross section (Qion,max) with polarizability is studied. A linear relationship is observed between these quantities indicating the consistency and reliability of the present Qion data. The targets studied are important for industrial applications, radiation biology, and astrophysics.

The Effect of Temporary Cement Cleaning Methods on the Retention of Crowns.

PURPOSE: To evaluate the effect of temporary cement cleaning methods on the retention of cemented crowns using zinc phosphate cement and resin-modified glass ionomer cement. MATERIALS AND METHODS: Forty titanium specimens were fabricated to simulate prepared molars with minimally retentive taper. The Ni-Cr cast crowns were fabricated, temporarily cemented, and separated. The specimens were divided into four groups according to the temporary cement cleaning method (n = 10) as follows: control group (no temporary cementation), orange solvent group, ultrasonic cleaning group, and air-abrasion group. After the cleaning procedures, the specimens were cemented with definitive cements (zinc phosphate cement and resin-modified glass ionomer, RMGI, cement) and subjected to thermocycling (5000 cycles, 5-55°C, dwell time, 10 seconds). The tensile bond strength of each specimen was measured using a universal testing machine, and the results were analyzed using the Kruskal-Wallis and Mann-Whitney U test (α = 0.05). RESULTS: When cemented with zinc phosphate cement, the statistical analysis showed that the value of the air-abrasion group was significantly higher than those of the other groups (p < 0.01). There was no statistically significant difference among the other groups. When cemented with RMGI cement, the air-abrasion group showed the lowest value, and the control group showed the highest value (p < 0.01). The difference between the ultrasonic cleaning group and the orange solvent group was not statistically significant. CONCLUSION: The use of temporary cement did not have a significant influence on retention of permanently cemented crowns when zinc phosphate cement was used for permanent cementation. Airborne-particle abrasion after provisional cementation improved retention of crowns cemented with zinc phosphate cement; however, the use of temporary cement significantly decreased retention of permanently cemented crowns when RMGI cement was used regardless of the temporary cement cleaning method.

Erratum to: PD-1 deficiency protects experimental colitis via alteration of gut microbiota.

The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 50(11): 578-583 titled "PD-1 deficiency protects experimental colitis via alteration of gut microbiota."

The Root of Atractylodes macrocephala Koidzumi Prevents Obesity and Glucose Intolerance and Increases Energy Metabolism in Mice.

Targeting energy expenditure offers a strategy for treating obesity more effectively and safely. In previous studies, we found that the root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on obesity and glucose intolerance by examining energy metabolism in skeletal muscle and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body weight gain, hepatic lipid levels and serum total cholesterol levels, but did not modify food intake. Fasting serum glucose, serum insulin levels and glucose intolerance were all improved in ARA treated mice. Furthermore, ARA increased peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) expression, and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle tissues, and also prevented skeletal muscle atrophy. In addition, the numbers of brown adipocytes and the expressions of PGC1α and uncoupling protein 1 (UCP1) were elevated in the brown adipose tissues of ARA treated mice. Our results show that ARA can prevent diet-induced obesity and glucose intolerance in C5BL/6 mice and suggests that the mechanism responsible is related to the promotion of energy metabolism in skeletal muscle and brown adipose tissues.

PD-1 deficiency protects experimental colitis via alteration of gut microbiota.

Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 (PD-1-/-) did not develop colon inflammation. Interestingly, PD-1-/- mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of PD-1-/- mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that PD-1-/- mice had altered composition of gut microbiota with significant reduction in Rikenellaceae family. These altered colon bacteria of PD-1-/- mice induced less amount of inflammatory mediators from colon epithelial cells, including interleukin (IL)-6, and inflammatory chemokines. Taken together, our study indicates that PD-1 expression is involved in the resistance to experimental colitis through altered bacterial communities of colon. [BMB Reports 2017; 50(11): 578-583].

Human bipedalism and body-mass index.

Body-mass index, abbreviated as BMI and given by M/H 2 with the mass M and the height H, has been widely used as a useful proxy to measure a general health status of a human individual. We generalise BMI in the form of M/H p and pursue to answer the question of the value of p for populations of animal species including human. We compare values of p for several different datasets for human populations with the ones obtained for other animal populations of fish, whales, and land mammals. All animal populations but humans analyzed in our work are shown to have p ≈ 3 unanimously. In contrast, human populations are different: As young infants grow to become toddlers and keep growing, the sudden change of p is observed at about one year after birth. Infants younger than one year old exhibit significantly larger value of p than two, while children between one and five years old show p ≈ 2, sharply different from other animal species. The observation implies the importance of the upright posture of human individuals. We also propose a simple mechanical model for a human body and suggest that standing and walking upright should put a clear division between bipedal human (p ≈ 2) and other animals (p ≈ 3).

Cinnamomum cassia Prevents High-Fat Diet-Induced Obesity in Mice through the Increase of Muscle Energy.

The cortex of Cinnamomum cassia Presl (Cinnamomi Cortex: CC) has commonly been used for weight control in traditional medicines, but without a scientific basis. Therefore, this study was undertaken to investigate the anti-obesity effect of CC extract in a high-fat diet (HFD)-induced obese mouse model and in C2C12 mouse skeletal muscle cells. Male C57BL/6 mice were fed a normal diet or a HFD for 16 consecutive weeks, and orally administered CC extract (100 or 300[Formula: see text]mg/kg) or metformin (250[Formula: see text]mg/kg; positive control) daily for 16 weeks. CC extract administration significantly decreased body weights, food intakes, and serum levels of glucose, insulin, total cholesterol and ALT levels, prevented oral glucose tolerance and insulin resistance, inhibited the protein expressions of MyHC and PGC1[Formula: see text] and the phosphorylation of AMPK, suppressed lipid accumulation in liver, decreased adipocyte size and increased muscle mass in obese mice. For this in vitro study, C2C12 myoblasts were differentiated into the myotubes for five days, and then treated with CC extract (0.1 or 0.2[Formula: see text]mg/ml) for 24[Formula: see text]h. CC extract significantly increased ATP levels by increasing the mRNA expressions of mitochondrial biogenesis-related factors, such as, PGC1[Formula: see text], NRF-1, and Tfam, and the phosphorylations of AMPK and ACC. Our results suggest CC extract controls weight gain in obese mice by inhibiting lipid accumulation and increasing energy expenditure, and that its action mechanism involves the up-regulation of mitochondrial biogenesis in skeletal muscle cells.