PMID- 36467351
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221206
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 10
IP  - 21
DP  - 2022 Nov
TI  - Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory 
      infiltration, and hepatic lipid accumulation in obese mice.
PG  - 1172
LID - 10.21037/atm-22-5145 [doi]
LID - 1172
AB  - BACKGROUND: Obesity, which results from a caloric intake and energy expenditure 
      imbalance, is highly prevalent worldwide. Cathepsin S (CTSS), which is a cysteine 
      protease, is elevated in obesity and may regulate a variety of physiological 
      processes. This study sought to investigate the functional role of CTSS in 
      obesity. METHODS: Mice were administrated 60 mg/kg of RO5444101 in vivo and fed a 
      high-fat diet (HFD) to induce obesity. The weights of the mice fed a normal-chow 
      diet and a HFD were measured. The expression levels of total triglycerides (TG), 
      total cholesterol (TC), aspartate aminotransferase (AST), alanine 
      aminotransferase (ALT), and monocyte chemoattractant protein-1 (MCP-1) were 
      assessed using appropriate corresponding assay kits. Reverse 
      transcription-quantitative polymerase chain reaction (RT-qPCR) was used to 
      estimate the messenger ribonucleic acid (mRNA) expression of CTSS in the serum 
      and the release of M1- and M2-type cytokines, and western blot was used to 
      measure the phosphorylated-nuclear factor kappaB (NF-kappaB) p65 and NF-kappaB p65 
      proteins. The mRNA and protein expressions of sterol regulatory element-binding 
      protein 1 (SREBP1), fatty acid synthase (FASN), leptin, and adiponectin were also 
      evaluated by RT-qPCR and western blot. Further, hematoxylin and eosin (H&E), 
      immunohistochemical, and red oil O staining were employed to detect the 
      pathological changes of the epididymal white adipose tissue (eWAT), the 
      macrophage infiltration in the eWAT, and lipid accumulation, respectively. 
      RESULTS: We found that CTSS was elevated in the plasma, visceral adipose, and 
      liver tissues of the obese mice. After the administration of 60 mg/kg of 
      RO5444101, the weight of the obese mice decreased, insulin resistance was 
      inhibited, and adipocyte formation was suppressed. The CTSS inhibitor also 
      decreased the level of macrophage infiltration in the eWAT, MCP-1 expression, and 
      the release of M1- and M2-type cytokines in the HFD-induced mice. The CTSS 
      inhibitor appeared to improve the hepatic function parameters and lipid 
      accumulation of the HFD-induced mice. The CTSS inhibitor also appeared to improve 
      the inflammatory damage in the HFD-induced mice. CONCLUSIONS: CTSS inhibitor 
      helped to protect against HFD-induced adipogenesis, inflammatory infiltration, 
      and hepatic lipid accumulation in obese mice.
CI  - 2022 Annals of Translational Medicine. All rights reserved.
FAU - Zheng, Jing
AU  - Zheng J
AD  - Department of Endocrinology, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, China.
FAU - Zhuang, Huijun
AU  - Zhuang H
AD  - Department of Endocrinology, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, China.
FAU - Zhang, Tian
AU  - Zhang T
AD  - Guizhou Medical University, Guiyang, China.
FAU - Wang, Yanni
AU  - Wang Y
AD  - Guizhou Medical University, Guiyang, China.
FAU - Ran, Ting
AU  - Ran T
AD  - Guizhou Medical University, Guiyang, China.
FAU - He, Juan
AU  - He J
AD  - Department of Endocrinology, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, China.
FAU - Han, Na
AU  - Han N
AD  - Department of Endocrinology, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, China.
FAU - Duan, Juan
AU  - Duan J
AD  - Department of Traditional Chinese Medicine, Health Center of Hongqi Town, Zhuhai, 
      China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9708477
OTO - NOTNLM
OT  - Obesity
OT  - adipogenesis
OT  - cathepsin S inhibitor (CTSS inhibitor)
OT  - inflammatory infiltration
OT  - lipid accumulation
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-5145/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2022/12/06 06:00
MHDA- 2022/12/06 06:01
PMCR- 2022/11/01
CRDT- 2022/12/05 04:23
PHST- 2022/09/23 00:00 [received]
PHST- 2022/10/31 00:00 [accepted]
PHST- 2022/12/05 04:23 [entrez]
PHST- 2022/12/06 06:00 [pubmed]
PHST- 2022/12/06 06:01 [medline]
PHST- 2022/11/01 00:00 [pmc-release]
AID - atm-10-21-1172 [pii]
AID - 10.21037/atm-22-5145 [doi]
PST - ppublish
SO  - Ann Transl Med. 2022 Nov;10(21):1172. doi: 10.21037/atm-22-5145.