Brown and Beige Adipocytes: Effects of Inflammation and Nutritional Intervention

Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue (BAT) have not been studied. In addition, in vitro and in vivo studies have shown that bioactive food components can contribute to obesity prevention; however, very few bioactive food components have been studied for their beneficial effects in promoting development and function of brown and beige adipocytes. This dissertation reports that (1) mRNA of PRRs and inflammatory cytokines/chemokines are upregulated in the BAT of both diet induced obesity mice model and ob/ob mice model; (2) activation of PRRs induces activation of NF-κB and MAPK signaling pathways, leading to upregulation of the proinflammatory genes, MCP- 1, IL-6, RANTES, and TNF-α, in mature brown adipocytes; (3) activation of PRRs suppresses UCP-1 expression, leading to decreased mitochondrial respiration and thermogenesis in mature brown adipocytes; (4) chronic activation of PRRs reduces adipogenesis and suppresses expression of brown-specific genes in both classic brown adipocytes and multipotent stem cells. This dissertation further demonstrates that naringenin, a flavanone mainly found in citrus fruits, enhances thermogenic activation in isoproterenol-stimulated 3T3-L1 adipocytes through PKA/p38 MAPK pathways. The results suggest that PRR-mediated inflammation in brown adipocytes may be a potential target for regulating BAT development and function for obesity treatment and prevention. Dietary bioactive compounds, such as naringenin, could be beneficial in promoting functional BAT, thereby contributing to energy expenditure

Non-Local and Quantum Advantages in Network Coding for Multiple Access Channels

Devising efficient communication in a network consisting of multiple transmitters and receivers is a problem of immense importance in communication theory. Interestingly, resources in the quantum world have been shown to be very effective in enhancing the performance of communication networks. In this work, we study entanglement-assisted communication over classical network channels. When there is asymmetry such that noise introduced by the channel depends on the input alphabets, non communicating senders may exploit shared entangled states to overcome the noise. We consider multiple access channels, an essential building block for many complex networks, and develop an extensive framework for n-senders and 1-receiver multiple access channels based on nonlocal games. We obtain generic results for computing correlation assisted sum-capacities of these channels. The considered channels introduce less noise on winning and more noise on losing the game, and the correlation assistance is classified as local (L), quantum (Q), or no-signaling (NS). Furthermore, we consider a broad class of multiple access channels such as depolarizing ones that admix a uniform noise with some probability and prove general results on their sum-capacities. Finally, we apply our analysis to three specific depolarizing multiple access channels based on Clauser-Horne-Shimony-Holt, magic square, and Mermin-GHZ nonlocal games. In all three cases we find significant enhancements in sum-capacities on using nonlocal correlations. We obtain either exact expressions for sum-capacities or suitable upper and lower bounds on them. The general framework developed in this work has much wider applicability and the specificity studied in details are some illustrative examples to compare with recent studies in this direction.Comment: Comments are welcome (15 pages, 7 figures

Developing General Literacy Ability and Intercultural Sensitivity through English Literacy Instruction: Using Global Literature for Korean EFL Learners

This study explored L2 literacy ability and intercultural sensitivity of Korean late elementary to early middle school students learning English as a foreign language. This study investigated the latent variable structure of L2 literacy abilities, including fluency, vocabulary, reading comprehension, and writing abilities, and intercultural sensitivity which involves interaction engagement, respect for cultural differences, interaction confidence, interaction enjoyment, and interaction attentiveness. It also examined the effects of reading global literature in literature-based instruction on overall L2 literacy ability and intercultural sensitivity development. The present study employed two different types of research design: a non-experimental, correlational design and a quasi-experimental research design. One hundred twenty-two 5th and 6th grade elementary students and one hundred forty 7th and 8th graders in middle school in Korea participated in this study. Among the 262 participants, 131 students from each grade were assigned to the treatment groups, and remaining 131 participants were in the control groups. The treatment group received 39 sessions of reading global literature in thirteen weeks; the control group did not receive any treatment in this study. Before and after the experiment period, all participants took pretests and posttests using the same instruments. Measurement instruments of this study consisted of two main parts: general literacy tests and the intercultural sensitivity scale. Instruments for this study measured text-level literacy development processes: fluency, vocabulary, reading comprehension, and writing. In addition, intercultural sensitivity was measured using with a 5-point Likert scale. The results of confirmatory factor analysis indicated one measurement model of L2 general literacy ability and intercultural sensitivity; these two latent factors are correlated with each other. In addition, four indicators of literacy ability (fluency, vocabulary, reading comprehension, and writing) were strong predictors of L2 learners' literacy achievement. Likewise, four indicators (interaction engagement, respect for cultural differences, interaction confidence, and interaction attentiveness) were highly correlated to intercultural sensitivity, but interaction enjoyment was not correlated to intercultural sensitivity. Therefore, interaction enjoyment was removed from the measurement model of literacy and intercultural sensitivity. This final model was used to analyze the post-test data across different groups, grade levels, and genders in order to find the effects of reading global literature. The latent mean analysis with the measurement model between literacy ability and intercultural sensitivity across control and treatment groups shows positive effects of reading global literature on L2 learners' development of literacy ability and intercultural sensitivity. The study results provided support for reading global literature as an effective and powerful instructional method to improve L2 learners' literacy ability and intercultural sensitivity. The students in the treatment group were more interculturally sensitive and outperformed the control group in L2 literacy achievement. In particular, there were some differences regarding intercultural sensitivity achievement for different grade levels, but there were no statistical differences between boys and girls in either their literacy ability or intercultural sensitivity development. The findings of this study have educational implications for teaching L2 with global literature to enhance L2 learners' intercultural sensitivity and literacy ability in their L2 learning

ボールミリング法で改質したβ-TCPセメントの諸特性への粉液比の影響

The authors have developed a β-tricalcium-phosphate (β-TCP) powder modified mechano-chemically through the application of a ball-milling process (mβ-TCP). The resulting powder can be used in a calcium-phosphate-cement (CPC). In this study, the effects of the powder-to-liquid ratio (P/L ratio) on the properties of the CPCs were investigated, and an appropriate P/L ratio that would simultaneously improve injectability and strength was clarified. The mβ-TCP cement mixed at a P/L ratio of 2.5 and set in air exhibited sufficient injectability until 20 min after mixing, and strength similar to or higher than that mixed at a P/L ratio of 2.0 and 2.78. Although the mβ-TCP cements set in vivo and in SBF were found to exhibit a lower strength than those set in air, it did have an appropriate setting time and strength for clinical applications. In conclusion, P/L ratio optimization successfully improved the strength of injectable mβ-TCP cement

強度と注入性に優れるβ-TCP基セメントへのジルコニア添加の効果

Injectable calcium phosphate cements (CPCs) exhibit many advantages as bone substitution materials. However, the strength of injectable CPCs after setting are often insufficient. In our previous studies, mechano-chemically modification of β-tricalcium phosphate cement powder through a planetary ball-milling process exhibited simultaneous improvement in the strength and injectability of CPC. Two plausible effects of this process are: changes in the CPC powder properties and zirconia abrasion powder contamination from the milling pot and balls. The objective of the present study is to separately evaluate these two effects on the strength and injectability of CPCs. The calculated injectability of the cement paste with and without the addition of zirconia powder were higher than 65% at 6 h after mixing. These values were much higher than that of the CPC paste without mechano-chemically modification, and similar to that of CPC with zirconia abrasion powder contamination. By contrast, the compression strength of the set CPC with zirconia powder additives were higher than that without the addition, and similar to that of CPC with zirconia abrasion powder contamination. These results suggest that the changes in the CPC powder properties due to mechano-chemically modification mainly affected the injectability of the CPC paste, and the zirconia abrasion powder contamination of the CPC powder affected the strength of the set CPC

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat–has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat– has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs

Arsenite exposure suppresses adipogenesis, mitochondrial biogenesis and thermogenesis via autophagy inhibition in brown adipose tissue

Arsenite, a trivalent form of arsenic, is an element that occurs naturally in the environment. Humans are exposed to high dose of arsenite through consuming arsenite-contaminated drinking water and food, and the arsenite can accumulate in the human tissues. Arsenite induces oxidative stress, which is linked to metabolic disorders such as obesity and diabetes. Brown adipocytes dissipating energy as heat have emerging roles for obesity treatment and prevention. therefore, understanding the pathophysiological role of brown adipocytes can provide effective strategies delineating the link between arsenite exposure and metabolic disorders. Our study revealed that arsenite significantly reduced differentiation of murine brown adipocytes and mitochondrial biogenesis and respiration, leading to attenuated thermogenesis via decreasing UCP1 expression. Oral administration of arsenite in mice resulted in heavy accumulation in brown adipose tissue and suppression of lipogenesis, mitochondrial biogenesis and thermogenesis.Mechanistically, arsenite exposure significantly inhibited autophagy necessary for homeostasis of brown adipose tissue through suppression of Sestrin2 and ULK1. These results clearly confirm the emerging mechanisms underlying the implications of arsenite exposure in metabolic disorders

Network-Level Structural Abnormalities of Cerebral Cortex in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion. © 2013 Lyoo et al