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Randomized Controlled Trial
. 2011;4(1):27-33.
doi: 10.1159/000324582. Epub 2011 Feb 16.

In vitro and in vivo effects of metformin on human adipose tissue adiponectin

Alessandra Zulian  1 , Raffaella Cancello, Andrea Girola, Luisa Gilardini, Luisella Alberti, Marina Croci, Giancarlo Micheletto, Piergiorgio Danelli, Cecilia Invitti
Affiliations
Randomized Controlled Trial

In vitro and in vivo effects of metformin on human adipose tissue adiponectin

Alessandra Zulian et al. Obes Facts. 2011.

Abstract

Objective: The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue. We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin.

Methods: For the in vitro study, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples from 5 non-diabetic obese patients were collected. For the in vivo investigation, 22 obese patients were randomly assigned to metformin+lifestyle (ML) or placebo+lifestyle (PL) intervention. SAT specimens and blood samples were collected before and after the intervention in both groups.

Results: In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants. In the in vivo study, a significant increase in adiponectin and a decreased expression of a macrophage activation marker (CD68) were observed only in SAT of the ML group.

Conclusion: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro. It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.

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Figures

Fig. 1
Fig. 1
a Mean ± SE mRNA expression levels of adiponectin gene in SAT (n = 5) and VAT (n = 5) explants. Black histograms represent the adiponectin expression in untreated explants. Grey histograms represent adiponectin expression after treatment with metformin (10 mmol/l) for 1 and 24 h. b Intracellular adiponectin protein content in SAT (n = 5) and VAT (n = 5) explants. Black histograms indicate the protein content in untreated explants. Grey histograms indicate the protein content after metformin (10 mmol/l) treatment in SAT and VAT explants for 1 and 24 h, respectively. Data are expressed as mean ± SE. A representative Western blot image of adiponectin and actin protein immunodetection is also shown. The adiponectin intracellular protein content was normalised by the intracellular actin protein content. c Adiponectin protein secretion in culture media of SAT (n = 5) and VAT (n = 5) explants untreated (black histograms) or treated with metformin (10 mmol/l) for 1 and 24 h (grey histograms). Data are expressed as mean ± SE (ng/ml/total protein content). AU = arbitrary units. *p < 0.05 treated explants versus untreated explants.
Fig 2
Fig 2
a Adiponectin and b CD68 mRNA expression levels in SAT collected from obese patients before (black histograms) and after (grey histograms) 3 months of metformin + lifestyle intervention (ML, n = 12) and placebo + lifestyle intervention (PL, n = 10). Data are expressed as mean ± SE. AU = arbitrary units. *p < 0.05 between data before intervention versus after intervention.
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