RARE DISEASE
Centrifugal lipodystrophy
Centrifugal lipodystrophy
Centrifugal lipodystrophy
Synonyms: Lipodystrophia centrifugalis abdominalis infantilis
Synonyms: Lipodystrophia centrifugalis abdominalis infantilis
Synonyms: Lipodystrophia centrifugalis abdominalis infantilis
Drug discovery
0
drugs
With orphan designations
Overview
Centrifugal lipodystrophy is a rare, acquired localized lipodystrophy characterized by asymptomatic or mildly tender, centrifugally expanding areas of subcutaneous fat loss, primarily affecting the lower trunk (groin/abdomen) and occasionally the upper trunk. Lesions exhibit hypopigmented depressions with erythematous borders and regional lymphadenopathy. It is typically self-resolving by adolescence and not associated with systemic metabolic complications [1][4][8].
Categories: rare endocrine diseases, rare skin diseases
Research Papers
13 drug discovery papers about Centrifugal lipodystrophy, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
13 drug discovery papers about Centrifugal lipodystrophy, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2024-03-14 | Lipodystrophia centrifugalis abdominals infantilis presenting as a giant ulceration and treatment with hydroxychloroquine and baricitinib
Summary Lipodystrophia centrifugalis abdominalis infantilis (LCAI) is a localised atrophic disease. It is characterised by a depression with a periphery of erythema present on the lower abdomen and/or the groin region, axilla or neck. The depressed lesions could enlarge centrifugally to the neighbouring areas. Ulceration is a rare manifestation of this disease. In this study, we reported a case of LCAI presented with recurrent giant ulcerations on the abdomen, and was eventually successfully treated with hydroxychloroquine and baritinib.
2023-05-25 | Beclin1-Deficient Adipocytes Promote Tumor Progression by YAP/TAZ-dependent Adipocyte Transformation
Abstract Adipocytes are crucial components of the tumor microenvironment (TME) that play a prominent role in supporting tumor growth. However, the characteristics of cancer-associated adipocytes (CAAs) that contribute to the pro-tumorigenic niche remain to be fully established. Here, we used adipocyte-specific Beclin1 KO (BaKO) mice to investigate the role of maladaptive adipocytes in promoting tumor progression. BECN1-deficient adipocytes exhibited downregulation of adipogenic markers and activation of YAP/TAZ signaling, similar to the traits observed in CAAs. Thus, we generated adipocyte-specific Becn1/Yap1/Taz KO mice, which exhibit markedly restored phenotypes in adipose tissue, resulting in tumor regression compared to that in BaKO. Further, we observed dysregulation of the BECN1-YAP/TAZ axis in the adipose tissue of mice fed a high-fat diet (HFD). Treatment with the YAP/TAZ inhibitor, verteporfin, suppressed tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Our findings provide insights into CAA formation and its significance in determining malignant TME, thereby suggesting a potential dual therapeutic strategy simultaneously targeting adipocyte homeostasis and cancer growth.
2022-11-04 | Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.
This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.
2016-10-15 | Case of lipodystrophia centrifugalis abdominalis infantilis successfully treated with topical application of tacrolimus
The Journal of DermatologyVolume 44, Issue 4 p. e68-e69 Letter to the Editor Case of lipodystrophia centrifugalis abdominalis infantilis successfully treated with topical application of tacrolimus Hideo Hashizume, Corresponding Author Hideo Hashizume hihashiz0001@mac.com Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanCorrespondence: Hideo Hashizume, M.D., Ph.D., Department of Dermatology, Shimada Municipal Hospital, 1200-5 Noda, Shimada, Shizuoka 427-8502, Japan. Email: hihashiz0001@mac.comSearch for more papers by this authorReiko Kageyama, Reiko Kageyama Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanSearch for more papers by this author Hideo Hashizume, Corresponding Author Hideo Hashizume hihashiz0001@mac.com Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanCorrespondence: Hideo Hashizume, M.D., Ph.D., Department of Dermatology, Shimada Municipal Hospital, 1200-5 Noda, Shimada, Shizuoka 427-8502, Japan. Email: hihashiz0001@mac.comSearch for more papers by this authorReiko Kageyama, Reiko Kageyama Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanSearch for more papers by this author First published: 15 October 2016 https://doi.org/10.1111/1346-8138.13638Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume44, Issue4April 2017Pages e68-e69 RelatedInformation
2015-12-19 | Targeting senescent cells enhances adipogenesis and metabolic function in old age
Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.
small molecules
2024-03-14 | Lipodystrophia centrifugalis abdominals infantilis presenting as a giant ulceration and treatment with hydroxychloroquine and baricitinib
Summary Lipodystrophia centrifugalis abdominalis infantilis (LCAI) is a localised atrophic disease. It is characterised by a depression with a periphery of erythema present on the lower abdomen and/or the groin region, axilla or neck. The depressed lesions could enlarge centrifugally to the neighbouring areas. Ulceration is a rare manifestation of this disease. In this study, we reported a case of LCAI presented with recurrent giant ulcerations on the abdomen, and was eventually successfully treated with hydroxychloroquine and baritinib.
2023-05-25 | Beclin1-Deficient Adipocytes Promote Tumor Progression by YAP/TAZ-dependent Adipocyte Transformation
Abstract Adipocytes are crucial components of the tumor microenvironment (TME) that play a prominent role in supporting tumor growth. However, the characteristics of cancer-associated adipocytes (CAAs) that contribute to the pro-tumorigenic niche remain to be fully established. Here, we used adipocyte-specific Beclin1 KO (BaKO) mice to investigate the role of maladaptive adipocytes in promoting tumor progression. BECN1-deficient adipocytes exhibited downregulation of adipogenic markers and activation of YAP/TAZ signaling, similar to the traits observed in CAAs. Thus, we generated adipocyte-specific Becn1/Yap1/Taz KO mice, which exhibit markedly restored phenotypes in adipose tissue, resulting in tumor regression compared to that in BaKO. Further, we observed dysregulation of the BECN1-YAP/TAZ axis in the adipose tissue of mice fed a high-fat diet (HFD). Treatment with the YAP/TAZ inhibitor, verteporfin, suppressed tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Our findings provide insights into CAA formation and its significance in determining malignant TME, thereby suggesting a potential dual therapeutic strategy simultaneously targeting adipocyte homeostasis and cancer growth.
2022-11-04 | Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.
This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.
2016-10-15 | Case of lipodystrophia centrifugalis abdominalis infantilis successfully treated with topical application of tacrolimus
The Journal of DermatologyVolume 44, Issue 4 p. e68-e69 Letter to the Editor Case of lipodystrophia centrifugalis abdominalis infantilis successfully treated with topical application of tacrolimus Hideo Hashizume, Corresponding Author Hideo Hashizume hihashiz0001@mac.com Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanCorrespondence: Hideo Hashizume, M.D., Ph.D., Department of Dermatology, Shimada Municipal Hospital, 1200-5 Noda, Shimada, Shizuoka 427-8502, Japan. Email: hihashiz0001@mac.comSearch for more papers by this authorReiko Kageyama, Reiko Kageyama Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanSearch for more papers by this author Hideo Hashizume, Corresponding Author Hideo Hashizume hihashiz0001@mac.com Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanCorrespondence: Hideo Hashizume, M.D., Ph.D., Department of Dermatology, Shimada Municipal Hospital, 1200-5 Noda, Shimada, Shizuoka 427-8502, Japan. Email: hihashiz0001@mac.comSearch for more papers by this authorReiko Kageyama, Reiko Kageyama Department of Dermatology, Shimada Municipal Hospital, Shimada, JapanSearch for more papers by this author First published: 15 October 2016 https://doi.org/10.1111/1346-8138.13638Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume44, Issue4April 2017Pages e68-e69 RelatedInformation
2015-12-19 | Targeting senescent cells enhances adipogenesis and metabolic function in old age
Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.
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