Determining residual adipose tissue characteristics with MRI in patients with various subtypes of lipodystrophy

Altay, Canan; Seçil, Mustafa; Demir, Tevfik; Atik, Tahir; Akıncı, Gülçin; Kutbay, Nilüfer Özdemir; Temeloğlu, Ela; Şimşir, Ilgın Yıldırım; Özışık, Seçil; Demir, Leyla; Eren, Erdal; Tuna, Emine Burçin; Aytaç, Hasibe; Önay, Hüseyin; Akıncı, Barış

doi:10.5152/dir.2017.17019

Cited by 25 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this, we observed a more modest reduction in Bscl2 expression in the IFP, in contrast to other adipose tissues in Ad-B2 (−/−) mice which showed a near-complete ablation of Bscl2 expression. This adds to existing evidence that so-called “mechanical” WAT depots may differ from other depots, including the observation that this type of WAT is almost entirely absent in CGL2 patients but preserved in other forms of CGL [34] , [40] . This type of WAT remains poorly understood but has been strongly implicated in joint disease [41] .…”

Section: Discussionmentioning

confidence: 53%

“…In contrast to tibial MAT but similar to vertebral MAT, we found that the IFP in the knee joint was largely preserved in Ad-B2 (−/−) mice. This depot is almost completely ablated in global seipin knockout mice ( Figure 3 H) and in CGL2 patients [40] . This strongly implies that the Adiponectin-Cre poorly targets this depot, at least early in adipogenesis, rather than that these adipocytes are unaffected by the absence of seipin.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Adipose specific disruption of seipin causes early-onset generalised lipodystrophy and altered fuel utilisation without severe metabolic disease

Mcilroy

Suchacki

Roelofs

et al. 2018

Molecular Metabolism

View full text Add to dashboard Cite

ObjectiveMutations to the BSCL2 gene disrupt the protein seipin and cause the most severe form of congenital generalised lipodystrophy (CGL). Affected individuals exhibit a near complete loss of white adipose tissue (WAT) and suffer from metabolic disease. Seipin is critical for adipocyte development in culture and mice with germline disruption to Bscl2 recapitulate the effects of BSCL2 disruption in humans. Here we examined whether loss of Bscl2 specifically in developing adipocytes in vivo is sufficient to prevent adipose tissue development and cause all features observed with congenital BSCL2 disruption.MethodsWe generated and characterised a novel mouse model of Bscl2 deficiency in developing adipocytes (Ad-B2(−/−)) using the adipose-specific Adiponectin-Cre line.ResultsWe demonstrate that Ad-B2(−/−) mice display early onset lipodystrophy, in common with congenital Bscl2 null mice and CGL2 patients. However, glucose intolerance, insulin resistance, and severe hepatic steatosis are not apparent. Food intake and energy expenditure are unchanged, but Ad-B2(−/−) mice exhibit significantly altered substrate utilisation. We also find differential effects of seipin loss between specific adipose depots revealing new insights regarding their varied characteristics. When fed a high-fat diet, Ad-B2(−/−) mice entirely fail to expand adipose mass but remain glucose tolerant.ConclusionsOur findings demonstrate that disruption of Bscl2 specifically in developing adipocytes is sufficient to cause the early-onset generalised lipodystrophy observed in patients with mutations in BSCL2. However, this significant reduction in adipose mass does not cause the overt metabolic dysfunction seen in Bscl2 knockout mice, even following a high-fat diet challenge.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 92%

Adipose specific disruption of seipin causes early-onset generalised lipodystrophy and altered fuel utilisation without severe metabolic disease

Mcilroy

Suchacki

Roelofs

et al. 2018

Molecular Metabolism

View full text Add to dashboard Cite

show abstract

“…In humans, congenital generalized lipodystrophy (CGL), which is an autosomal recessive disease, shed light on the research of BMAs. Different gene mutations have been identified in four subtypes of CGL: 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), Berardinelli-Seip congenital lipodystrophy 2 (BSCL2 or seipin), caveolin 1 (CAV1) and polymerase I and transcript release factor (PTRF) mutation are responsible for CGL1, CGL2, CGL3, and CGL4, respectively ( 139 ). Despite the nearly complete lack of peripheral WAT in patients with CGL, BMAs are well preserved in patients with CAV1 (CGL3) or PTRF (CGL4) mutation.…”

Section: Bmas Could Be the Potential Target For Bone Metastasismentioning

confidence: 99%

Bone Marrow Adipocyte: An Intimate Partner With Tumor Cells in Bone Metastasis

Luo

2018

Front. Endocrinol.

View full text Add to dashboard Cite

The high incidences of bone metastasis in patients with breast cancer, prostate cancer and lung cancer still remains a puzzling issue. The “seeds and soil” hypothesis suggested that bone marrow (soil) may provide a favorable “niche” for tumor cells (seed). When seeking for effective ways to prevent and treat tumor bone metastasis, most researchers focus on tumor cells (seed) but not the bone marrow microenvironment (soil). In reality, only a fraction of circulating tumor cells (CTCs) could survive and colonize in bone. Thus, the bone marrow microenvironment could ultimately determine the fate of tumor cells that have migrated to bone. Bone marrow adipocytes (BMAs) are abundant in the bone marrow microenvironment. Mounting evidence suggests that BMAs may play a dominant role in bone metastasis. BMAs could directly provide energy for tumor cells, enhance the tumor cell proliferation, and resistance to chemotherapy and radiotherapy. BMAs are also known for releasing some inflammatory factors and adipocytokines to promote or inhibit bone metastasis. In this review, we made a comprehensive summary for the interaction between BMAs and bone metastasis. More importantly, we discussed the potentially promising methods for the prevention and treatment of bone metastasis. Genetic disruption and pharmaceutical inhibition may be effective in inhibiting the formation and pro-tumor functions of BMAs.

show abstract

“…Compound heterozygous or homozygous pathogenic variants with low levels of in vitro enzyme activity have also been reported (7,13). Although patients with CGL1 lack metabolically active adipose tissue, the preservation of residual mechanical adipose tissue in the palms, soles, scalp, orbital and periarticular regions and the perineum is clinically apparent (14,15). CGL2 (OMIM #269700) is caused by pathogenic variants of the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene (16), which encodes the transmembrane protein seipin.…”

Section: Congenital Generalized Lipodystrophymentioning

confidence: 99%

Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People

Özen

Akıncı

Oral

2020

Jcrpe

View full text Add to dashboard Cite

Lipodystrophy is a heterogeneous group of disorders characterized by lack of body fat in characteristic patterns, which can be genetic or acquired. Lipodystrophy is associated with insulin resistance that can develop in childhood and adolescence, and usually leads to severe metabolic complications. Diabetes mellitus, hypertriglyceridemia, and hepatic steatosis ordinarily develop in these patients, and most girls suffer from menstrual abnormalities. Severe complications develop at a relatively young age, which include episodes of acute pancreatitis, renal failure, cirrhosis, and complex cardiovascular diseases, and all of these are associated with serious morbidity. Treatment of lipodystrophy consists of medical nutritional therapy, exercise, and the use of anti-hyperglycemic and lipid-lowering agents. New treatment modalities, such as metreleptin replacement, promise much in the treatment of metabolic abnormalities secondary to lipodystrophy. Current challenges in the management of lipodystrophy in children and adolescents include, but are not limited to: (1) establishing specialized centers with experience in providing care for lipodystrophy presenting in childhood and adolescence; (2) optimizing algorithms that can provide some guidance for the use of standard and novel therapies to ensure adequate metabolic control and to prevent complications; (3) educating patients and their parents about lipodystrophy management; (4) improving patient adherence to chronic therapies; (5) reducing barriers to access to novel treatments; and (5) improving the quality of life of these patients and their families.

show abstract

Determining residual adipose tissue characteristics with MRI in patients with various subtypes of lipodystrophy

Cited by 25 publications

References 35 publications

Adipose specific disruption of seipin causes early-onset generalised lipodystrophy and altered fuel utilisation without severe metabolic disease

Adipose specific disruption of seipin causes early-onset generalised lipodystrophy and altered fuel utilisation without severe metabolic disease

Bone Marrow Adipocyte: An Intimate Partner With Tumor Cells in Bone Metastasis

Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People

Contact Info

Product

Resources

About