Cathepsin L activity controls adipogenesis and glucose tolerance

Yang, Min; Zhang, Y; Pan, Jiehong; Sun, Jiusong; Liu, Jian; Libby, Peter; Sukhova, Galina K.; Doria, Alessandro; Katunuma, Nobuhiko; Peroni, Odile D.; Guerre-Millo, Michéle; Kahn, Barbara B.; Clément, Karine; Shi, Guo‐Ping

doi:10.1038/ncb1623

Cited by 174 publications

(168 citation statements)

References 30 publications

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“…*P < 0.05; **P < 0.01; ***P < 0.001. important component of ECM microenvironments that inform the functional behavior of adipocytes, skeletal muscle myofibers, and pancreatic islet cells. Col5a3 ablation effects on WAT/adipocytes are consistent with recent studies in which other ECM defects affected adipocyte biology (16,23,24), thus underscoring an emerging view of ECM as a major determinant of adipocyte behavior. Additionally, absence of α3(V) chains in 3T3-L1 preadipocyte cultures, but induction of such chains upon adipocytic differentiation, is consistent with an adipocyte-specific dimension to α3(V) function.…”

Section: Figure 10supporting

confidence: 76%

α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues

Huang¹,

Ge²,

Wang³

et al. 2011

J. Clin. Invest.

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Section: Figure 10supporting

confidence: 76%

α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues

Huang¹,

Ge²,

Wang³

et al. 2011

J. Clin. Invest.

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“…Although leptin exists in both free and bound fractions, the bound form of leptin would be protected from degradation. Our hypothesis is supported by the impaired adipocyte differentiation and reduced weight gain observed in a diet-induced obese model in cathepsins L and K knockout mice and both display a lean phenotype (Funicello et al 2007, Yang et al 2007.…”

Section: Discussionsupporting

confidence: 63%

Cysteine cathepsin S processes leptin, inactivating its biological activity

Oliveira

Assis²,

Paschoalin³

et al. 2012

Journal of Endocrinology

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Leptin is a 16 kDa hormone mainly produced by adipocytes that plays an important role in many biological events including the regulation of appetite and energy balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and inflammation. The search for proteolytic enzymes capable of processing leptin prompted us to investigate the action of cysteine cathepsins on human leptin degradation. In this study, we observed high cysteine peptidase expression and hydrolytic activity in white adipose tissue (WAT), which was capable of degrading leptin. Considering these results, we investigated whether recombinant human cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass spectrometry analysis revealed that among the tested enzymes, cathepsin S exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel assay, we observed that the leptin fragments generated by cathepsin S digestion did not exhibit angiogenic action on endothelial cells and were unable to inhibit food intake in Wistar rats after intracerebroventricular administration. Taken together, these results suggest that cysteine cathepsins may be putative leptin activity regulators in WAT.

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“…The phenotypes of fat-induced CatE -/-mice displaying defective adipose tissue development are reminiscent of those of mice deficient in cathepsin L, a ubiquitously distributed cysteine protease [17], or cathepsin K, the osteoclast-and activated macrophage-specific cysteine protease [18] [19]. Fat-induced mice, deficient in either cathepsin L or cathepsin K, all display a lean phenotype and defective adipose tissue development.…”

Section: Discussionmentioning

confidence: 99%

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Kadowaki

Kido

Hatakeyama

et al. 2014

Biochemical and Biophysical Research Communications

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Running title: Fat-induced cathepsin E-deficient mice Key words: cathepsin E, high-fat diet, adipose tissue AbstractCathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE -/-) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE -/-mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE -/-mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE -/-mice. In fat-induced CatE -/-mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE -/-mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.

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Cathepsin L activity controls adipogenesis and glucose tolerance

Cited by 174 publications

References 30 publications

α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues

α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues

Cysteine cathepsin S processes leptin, inactivating its biological activity

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

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