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

Evodiamine Inhibits Insulin-Stimulated mTOR-S6K Activation and IRS1 Serine Phosphorylation in Adipocytes and Improves Glucose Tolerance in Obese/Diabetic Mice

Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes

ビタミン D オ タイシャスル シトクロム P450 ノ コウゾウ ト キノウ ノ カイセキ

京都大学0048新制・課程博士博士(農学)甲第10900号農博第1406号新制||農||890(附属図書館)学位論文||H16||N3911(農学部図書室)UT51-2004-G747京都大学大学院農学研究科食品生物科学専攻(主査)教授 井上 國世, 教授 大東 肇, 教授 伏木 亨学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDA

Phenolic compounds from leaves of Casimiroa edulis showed adipogenesis activity.

Casimiroa edulis is known as cochitzapotl, and it belongs to a species of tropical fruiting tree in the family Rutaceae, native to eastern Mexico and Central America south to Costa Rica. In this study, we isolated two furocoumarins and two polymethoxyflavones from leaves of C. edulis and evaluated the functions of glucose and lipid metabolism activity with 3T3-L1 adipocytes. We discovered that the addition of furocoumarins increased glucose uptake and lipid accumulation in 3T3-L1 adipocyte. These results suggest that furocoumarin compounds can be used as functional food-derived compounds, to regulate adipocyte functioning for the management of metabolic syndrome, which is associated with dysfunctions of glucose and lipid metabolism

Fact-Checking Cancer Information on Social Media in Japan: Retrospective Study Using Twitter

BackgroundThe widespread use of social media has made it easier for patients to access cancer information. However, a large amount of misinformation and harmful information that could negatively impact patients’ decision-making is also disseminated on social media platforms. ObjectiveWe aimed to determine the actual amount of misinformation and harmful information as well as trends in the dissemination of cancer-related information on Twitter, a representative social media platform. Our findings can support decision-making among Japanese patients with cancer. MethodsUsing the Twitter app programming interface, we extracted tweets containing the term “cancer” in Japanese that were posted between August and September of 2022. The eligibility criteria were the cancer-related tweets with the following information: (1) reference to the occurrence or prognosis of cancer, (2) recommendation or nonrecommendation of actions, (3) reference to the course of cancer treatment or adverse events, (4) results of cancer research, and (5) other cancer-related knowledge and information. Finally, we selected the top 100 tweets with the highest number of “likes.” For each tweet, 2 independent reviewers evaluated whether the information was factual or misinformation, and whether it was harmful or safe with the reasons for the decisions on the misinformation and harmful tweets. Additionally, we examined the frequency of information dissemination using the number of retweets for the top 100 tweets and investigated trends in the dissemination of information. ResultsThe extracted tweets totaled 69,875. Of the top 100 cancer-related tweets with the most “likes” that met the eligibility criteria, 44 (44%) contained misinformation, 31 (31%) contained harmful information, and 30 (30%) contained both misinformation and harmful information. Misinformation was described as Unproven (29/94, 40.4%), Disproven (19/94, 20.2%), Inappropriate application (4/94, 4.3%), Strength of evidence mischaracterized (14/94, 14.9%), Misleading (18/94, 18%), and Other misinformation (1/94, 1.1%). Harmful action was described as Harmful action (9/59, 15.2%), Harmful inaction (43/59, 72.9%), Harmful interactions (3/59, 5.1%), Economic harm (3/59, 5.1%), and Other harmful information (1/59, 1.7%). Harmful information was liked more often than safe information (median 95, IQR 43-1919 vs 75.0 IQR 43-10,747; P=.04). The median number of retweets for the leading 100 tweets was 13.5 (IQR 0-2197). Misinformation was retweeted significantly more often than factual information (median 29.0, IQR 0-502 vs 7.5, IQR 0-2197; P=.01); harmful information was also retweeted significantly more often than safe information (median 35.0, IQR 0-502 vs 8.0, IQR 0-2197; P=.002). ConclusionsIt is evident that there is a prevalence of misinformation and harmful information related to cancer on Twitter in Japan and it is crucial to increase health literacy and awareness regarding this issue. Furthermore, we believe that it is important for government agencies and health care professionals to continue providing accurate medical information to support patients and their families in making informed decisions

Effect of evodiamine on the mTOR-S6K signaling in the liver of mice treated with evodiamine.

<p>Western blot analysis for mTOR (A), S6K (B), Akt (C) and IRS1 (D) were done with tissue lysates (30–50 µg protein) of liver from the KK-Ay mice treated with evodiamine for 7 days. Phosphorylation levels of mTOR Ser2448, S6K Thr389, Akt Ser473 and IRS1 Ser636/639 were normalized to the total level of each protein. Data are expressed as mean±SEM (<i>n</i> = 5). **<i>p</i><0.01 <i>vs.</i> vehicle group.</p

Effect of evodiamine on the insulin-stimulated activation of mTOR-S6K signaling in differentiated adipocytes.

<p>After 3T3-L1 pre-adipocytes were differentiated into mature adipocytes, the cells were maintained in DMEM for 4 h and then stimulated by 20 nM insulin with or without 20 µM evodiamine for the indicated length of time. The cell lysates (15–30 µg protein) were analyzed for phosphorylation of mTOR Ser2448, S6K Thr389, IRS1 Ser636/639, Akt Ser473 and ERK Thr202/Tyr204 by Western blot analysis. Representative images of two independent experiments are shown.</p