PMID- 35366568
OWN - NLM
STAT- MEDLINE
DCOM- 20220524
LR  - 20240102
IS  - 1879-0054 (Electronic)
IS  - 0739-7240 (Linking)
VI  - 80
DP  - 2022 Jul
TI  - Effect of tetra-hydroxylated bile acid on size and insulin sensitivity of 
      subcutaneous adipocytes in healthy lean cats.
PG  - 106722
LID - S0739-7240(22)00013-3 [pii]
LID - 10.1016/j.domaniend.2022.106722 [doi]
AB  - Obesity leads to insulin resistance and is a major risk factor for the 
      development of diabetes mellitus in cats. Prevention of obesity and 
      obesity-induced insulin resistance is difficult, and reliable long-term 
      strategies are currently lacking. Retinoid-related orphan receptor gamma (RORgamma) 
      was recently identified as an important transcription factor in the development 
      of large insulin-resistant adipocytes in mice and humans. RORgamma negatively affects 
      adipocyte differentiation through expression of its target gene matrix 
      metalloproteinase 3 (MMP3) and promotes the development of large 
      insulin-resistant adipocytes. Preliminary studies in mice showed that RORgamma can be 
      inhibited by its ligand tetra-hydroxylated bile acid (THBA). In the present 
      study, serum THBA levels were determined in healthy and diabetic cats. Moreover, 
      potential side effects and the effects of THBA supplementation on adipocyte size, 
      mRNA expression of RORgamma, MMP3, interleukin 6, tumor necrosis factor alpha, 
      adiponectin and leptin in feline subcutaneous adipocytes and insulin sensitivity 
      were investigated in healthy normal weight cats. Thirteen healthy and 13 diabetic 
      cats were used for determination of serum THBA level, and six healthy 
      normal-weight cats were included in a feeding trial. Similar THBA levels were 
      determined in serum of healthy and diabetic cats. Supplementation of 5 mg/kg THBA 
      for 8 wk did not cause any negative effect on feeding behavior, general condition 
      and blood parameters of tested cats. It significantly reduced adipocyte size and 
      mRNA expression of MMP3, interleukin 6, and tumor necrosis factor alpha in 
      adipocytes, while mRNA expression of adiponectin significantly increased and mRNA 
      expression of RORgamma and leptin remained unchanged. Administration of THBA did not 
      influence fasting blood glucose levels or the response of cats to acute insulin 
      administration. Based on these results, THBA is palatable and is considered safe 
      for use in cats. It reduces expression of MMP3 and promotes the development of 
      small adipocytes with increased expression of adiponectin and reduced expression 
      of interleukin 6 and tumor necrosis factor alpha. Further studies are recommended to 
      evaluate the effect of THBA on adipocyte size and insulin sensitivity in obese 
      cats.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Rast, I T
AU  - Rast IT
AD  - Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of 
      Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
FAU - Zini, E
AU  - Zini E
AD  - Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of 
      Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland; Department of Animal 
      Medicine, Production and Health, University of Padova, Legnaro (PD), Italy; 
      AniCura Istituto Veterinario Novara, Granozzo con Monticello (NO), Italy.
FAU - Wolfrum, C
AU  - Wolfrum C
AD  - Laboratory of Translational Nutrition Biology, Swiss Federal Institute of 
      Technology Zurich, Schwerzenbach, Switzerland.
FAU - Lutz, T A
AU  - Lutz TA
AD  - Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, 
      Zurich, Switzerland.
FAU - Reusch, C E
AU  - Reusch CE
AD  - Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of 
      Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
FAU - Salesov, E
AU  - Salesov E
AD  - Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of 
      Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. Electronic address: 
      esalesov@vetclinics.uzh.ch.
LA  - eng
PT  - Journal Article
DEP - 20220223
PL  - United States
TA  - Domest Anim Endocrinol
JT  - Domestic animal endocrinology
JID - 8505191
RN  - 0 (Adiponectin)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Leptin)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Adiponectin
MH  - Animals
MH  - Bile Acids and Salts/metabolism
MH  - *Cat Diseases/metabolism
MH  - Cats
MH  - *Diabetes Mellitus/veterinary
MH  - Insulin/metabolism
MH  - *Insulin Resistance/physiology
MH  - Interleukin-6/pharmacology
MH  - Leptin
MH  - Matrix Metalloproteinase 3/metabolism/pharmacology
MH  - Mice
MH  - *Obesity/metabolism/veterinary
MH  - RNA, Messenger/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Adipocyte
OT  - Diabetes mellitus
OT  - Feline
OT  - Insulin sensitivity
OT  - Retinoid-related orphan receptor gamma
OT  - Tetra-hydroxylated bile acid
EDAT- 2022/04/03 06:00
MHDA- 2022/05/25 06:00
CRDT- 2022/04/02 20:09
PHST- 2021/07/29 00:00 [received]
PHST- 2022/02/16 00:00 [revised]
PHST- 2022/02/17 00:00 [accepted]
PHST- 2022/04/03 06:00 [pubmed]
PHST- 2022/05/25 06:00 [medline]
PHST- 2022/04/02 20:09 [entrez]
AID - S0739-7240(22)00013-3 [pii]
AID - 10.1016/j.domaniend.2022.106722 [doi]
PST - ppublish
SO  - Domest Anim Endocrinol. 2022 Jul;80:106722. doi: 10.1016/j.domaniend.2022.106722. 
      Epub 2022 Feb 23.