Update on the Pathophysiological Activities of the Cardiac Molecule Cardiotrophin-1 in Obesity

Table 1

Summary of the most relevant CT-1-mediated effects in vitro, in vivo, and in humans in adipose tissue and obesity.

Author [Ref.]	Year	Model	Exogenous treatment	Effects
In vitro
Natal et al. [13]	2008	Murine 3T3-L1 preadipocytes versus differentiated adipocytes	Not applicable	Upregulation of CT-1 levels in differentiated adipocytes and in response to proinflammatory molecules
Zvonic et al. [14]	2004	Murine 3T3-L1 preadipocytes and differentiated adipocytes	Recombinant human CT-1 (0.02–2 nM)	Dose- and time-dependent activation and nuclear translocation of STAT1, -3, -5A, and -5B as well as ERK1 and -2
In vivo
Zvonic et al. [14]	2004	7-week-old C57B1/6J mice	Recombinant human CT-1 at 0.5 microg/animal versus vehicle	Activation of MAPK, STAT-1, -3 in epididymal fat pads
López-Andrés et al. [55]	2012	Wistar rats	Treatment with rat recombinant CT-1 (20 μg/kg per day till 6 weeks) versus vehicle	Chronic treatment with CT-1 increases fibrosis within heart vessel and kidney as compared to controls
Moreno-Aliaga et al. [18]	2011	CT-1 knockout versus wild-type mice under normal diet, high-cholesterol diet, or streptozotocin- (STZ-) induced diabetes	Treatment with rat recombinant CT-1 (0.2 mg/kg per day for 6–10 days) versus vehicle	CT-1 knockout mice develop obesity, insulin resistance, and hypercholesterolemia despite a reduced caloric intake as compared to wild type.; Acute treatment with CT-1 decreased blood glucose in an insulin-independent manner as compared to vehicle.; Chronic treatment with CT-1 treatment reduced food intake, enhanced energy expenditure, and induced white adipose tissue remodeling as compared to vehicle
Humans
Natal et al. [13]	2008	Patients with metabolic syndrome (𝑛=43) versus healthy controls (𝑛=94)	Not applicable	Increased plasma levels of CT-1 in metabolic syndrome patients as compared to controls
Limongelli et al. [56]	2010	Triathletes versus matched controls (𝑛=20 per group)	Not applicable	During physical exercise, plasma levels of CT-1 were significantly increased as compared to levels at rest in triathletes
Jung et al. [58]	2008	White adolescents (aged 13 to 17 years) overweight (𝑛=37) versus normal weight controls (𝑛=35)	Not applicable	No increase in CT-1 plasma levels in overweight adolescents as compared to normal weight controls