{"id":8066,"date":"2023-12-04T14:08:55","date_gmt":"2023-12-04T05:08:55","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=8066"},"modified":"2023-12-05T09:54:05","modified_gmt":"2023-12-05T00:54:05","slug":"shimomura2023-12-4","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2023year\/shimomura2023-12-4","title":{"rendered":"Jihoon Shin, Atsunori Fukuhara, Iichiro Shimomura \u226aMetabolic Medicine\u226b <span>Chaperoning fat storage: the molecular basis of adiposity<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2023year\/shimomura2023-12-4\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p>Nature Communications<\/p>\n<p><em>Researchers from Osaka University find that <\/em><em>HSP47, a collagen-specific molecular chaperone, is a key determinant of body fat levels<\/em><\/p>\n<p class=\"figure\"><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2023\/11\/shin_efig1.png\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-8067 size-medium\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2023\/11\/shin_efig1-400x400.png?_t=1700798753\" alt=\"\" width=\"400\" height=\"400\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2023\/11\/shin_efig1-400x400.png 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2023\/11\/shin_efig1-150x150.png 150w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2023\/11\/shin_efig1-768x768.png 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2023\/11\/shin_efig1.png 900w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/a><br \/>Figure 1. Body fat levels vary due to physiological, pathological, environmental, hormonal, and genetic factors. Our study identifies HSP47 \u2013 abundant in fat tissues \u2013 as a key determinant of body adiposity. HSP47 expression increases with feeding, overeating, and obesity, and decreases with fasting, exercise, calorie restriction, bariatric surgery, and cachexia. It significantly correlates with body fat traits, such as body fat mass, BMI, waist, and hip circumferences, and is regulated by insulin and glucocorticoids. In humans, increased HSP47 gene expression by its intron or synonymous variants, is associated with higher body fat. Mice lacking HSP47 show significantly lower body fat. Mechanistically, HSP47 promotes collagen protein dynamics, including folding, secretion, and interaction with integrin, which activates FAK signaling and preserves PPAR\u03b3 protein from proteasomal degradation, partly related to MDM2. These findings highlight the significant role of HSP47 in body adiposity. This study provides valuable insights into the individual variability and differences in body adiposity traits observed in diverse circumstances.<\/p>\n<div class=\"TextBlock\">\n<p>We all know that weight gain and weight loss are not as simple as \u201ccalories in, calories out,\u201d given that countless factors affect body weight. Now, researchers from Japan have identified a gene that may serve as a master regulator of fat storage under a wide range of conditions.<\/p>\n<p>In a study published this month in <em>Nature Communications<\/em>, researchers from Osaka University have revealed that this single gene may be the key to body size.<\/p>\n<p>Whether a person is lean or fat depends on a host of factors, from activity levels to food intake, illness, living environment, and more. Family history also clearly plays a role, but the genetic basis of body weight is still poorly understood.<\/p>\n<p>\u201cFat is a unique tissue that is regulated by various nutritional, hormonal, and molecular factors,\u201d says lead author of the study Jihoon Shin. \u201cHowever, a unified genetic basis for its regulation remains elusive.\u201d<\/p>\n<p>To identify genetic factors responsible for fat deposition, the researchers analyzed gene expression data from fat tissue compared with other tissue types. The results showed that HSP47, a collagen-specific molecular chaperone, is a significant determinant of body fat levels.<\/p>\n<p>\u201cHSP47 is expressed at high levels in fat tissue and increases with obesity and greater food intake; in contrast, its expression level decreases with fasting, exercise, calorie restriction, bariatric surgery, and wasting syndrome,\u201d explains Iichiro Shimomura, senior author. \u201cIn addition, HSP47 expression correlates closely with fat mass, body mass index, waist circumference, and hip circumference.\u201d<\/p>\n<p>Importantly, the researchers found that insulin, a hormone associated with fat storage or fat loss, increases HSP47 expression levels; while conversely, glucocorticoids decrease HSP47 expression levels. In addition, high or low HSP47 expression was linked to high or low body fat levels in both humans and mice.<\/p>\n<p>\u201cThe findings from our study highlight the significant role that HSP47 plays in determining an individual\u2019s amount of body fat normally and in response to various factors such as disease or changing hormone levels,\u201d says Shin.<\/p>\n<p>The identification of HSP47 as a key factor influencing fat storage provides a clear genetic basis for overall body fat levels and energy use. Given the central role of HSP47 in this process, it is possible that alterations in this gene could create metabolic disturbances.<\/p>\n<\/div>\n<p>###<\/p>\n<p>The article, \u201cHSP47 levels determine the degree of body adiposity,\u201d was published in <em>Nature Communications<\/em> at DOI: <a href=\"https:\/\/doi.org\/10.1038\/s41467-023-43080-x\">10.1038\/s41467-023-43080-x<\/a>.<\/p>\n<p><strong>Summary:<\/strong> Researchers from Osaka University found that HSP47, a collagen-specific chaperone, is a key determinant of body fat levels. HSP47 expression levels are upregulated with obesity and greater food intake and decreased with fasting, exercise, calorie restriction, bariatric surgery, and wasting syndrome, suggesting that HSP47 modulation has a profound effect on fat storage.<\/p>\n<p><strong>Tweet 1<\/strong>: Jack Sprat could store no fat? #HSP47 expression is decreased with #fasting and #exercise but increased with #obesity and greater food intake, thereby regulating fat storage @osaka_univ_e<\/p>\n<p><strong>Primary Keyword<\/strong>: Health and medicine<br \/><strong>Additional Keywords<\/strong>: Obesity, Metabolic disorders, Cachexia, Molecular chaperones, Adipose tissue, Metabolism, Fat storage<\/p>\n<p><strong>Method of Research<\/strong>: Experimental study<\/p>\n<p><strong>Subject of Research<\/strong>: Animals<\/p>\n<div class=\"TextBlock\">\n<p>Title: \u201cHSP47 levels determine the degree of body adiposity\u201d<\/p>\n<\/div>\n<p>Journal: <em>Nature Communications<\/em><em><br \/><\/em>Authors: Jihoon Shin, Shinichiro Toyoda, Yosuke Okuno, Reiko Hayashi, Shigeki Nishitani, Toshiharu Onodera, Haruyo Sakamoto, Shinya Ito, Sachiko Kobayashi, Hirofumi Nagao, Shunbun Kita, Michio Otsuki, Atsunori Fukuhara, Kazuhiro Nagata, and Iichiro Shimomura<br \/>DOI: <a href=\"https:\/\/doi.org\/10.1038\/s41467-023-43080-x\">10.1038\/s41467-023-43080-x<\/a>.<\/p>\n<p>Funded by:<\/p>\n<p>Japan Society for the Promotion of Science (JSPS)<br \/>Front Runner of Future Diabetes Research (FFDR)<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Nature Communications Researchers from Osaka University find that HSP47, a collagen-specific  [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":8067,"parent":7833,"menu_order":41,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8066"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=8066"}],"version-history":[{"count":4,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8066\/revisions"}],"predecessor-version":[{"id":8078,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8066\/revisions\/8078"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/7833"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/8067"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=8066"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}