Limits...
Modifications of Human Subcutaneous ADMSC after PPARγ Activation and Cold Exposition.

Vargas D, Rosales W, Lizcano F - Stem Cells Int (2015)

Bottom Line: In the present study, we determined the effect of partial agonism of PPARγ and temperature reduction on phenotype and metabolic activity of ADMSCs from human adipose subcutaneous tissue.We found that adipocytes differentiated with total and partial agonists of PPARγ and exposed to 31°C are able to respond to cold significantly increasing the expression of thermogenic proteins such as UCP1, PGC1α, and CITED1, a marker of beige phenotype.Additionally, we found that adipocyte cells subjected to cold had a reduction in triglycerides and increased adiponectin levels.

View Article: PubMed Central - PubMed

Affiliation: Centro de Investigación Biomédica, CIBUS, Universidad de La Sabana, Km 7, Autopista Norte de Bogotá, 140013 Chía, Colombia.

ABSTRACT
Mesenchymal stem cells are a diverse population of cells with a wide range of potential therapeutic applications. In particular, cells from adipose tissue have the distinction of being easily accessible and contain a lot of stem cells. ADMSCs can be induced to mature adipocyte and activate the energy expenditure upon treatment with total PPARγ agonists. Additionally these cells may respond to cold by activating the thermogenic program. In the present study, we determined the effect of partial agonism of PPARγ and temperature reduction on phenotype and metabolic activity of ADMSCs from human adipose subcutaneous tissue. We found that adipocytes differentiated with total and partial agonists of PPARγ and exposed to 31°C are able to respond to cold significantly increasing the expression of thermogenic proteins such as UCP1, PGC1α, and CITED1, a marker of beige phenotype. Additionally, we found that adipocyte cells subjected to cold had a reduction in triglycerides and increased adiponectin levels. These data confirm the promising role of ADMSCs as a treatment for metabolic disorders since it is possible to induce them to mature adipocytes and modulate their phenotype toward a cell with high-energy expenditure and metabolic beneficial effect.

No MeSH data available.


Related in: MedlinePlus

Effect of cold on triglyceride levels in differentiated human adipocytes. (a) ADMSCs were obtained from human subcutaneous adipocytes differentiated and induced for 10 days with 1 μM of full agonist (Rosiglitazone) and 50 μM partial agonist (Telmisartan). Cells were maintained at 37°C or exposed to 31°C for 4 hours and after, staining was performed with Oil Red O. (b) Quantification of triglyceride levels is expressed as relative values. Statistical analysis was performed using ANOVA test. Data are expressed as mean ± SD of 3 independent experiments performed in triplicate. Differences were considered statistically significant at P < 0.05. Rosi (Rosiglitazone), Telmi (Telmisartan). ∗Differences between triglyceride levels of treatments with PPAR agonist in relation to control (induction of differentiation with basal medium). # indicates differences found between treatments.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4539182&req=5

fig1: Effect of cold on triglyceride levels in differentiated human adipocytes. (a) ADMSCs were obtained from human subcutaneous adipocytes differentiated and induced for 10 days with 1 μM of full agonist (Rosiglitazone) and 50 μM partial agonist (Telmisartan). Cells were maintained at 37°C or exposed to 31°C for 4 hours and after, staining was performed with Oil Red O. (b) Quantification of triglyceride levels is expressed as relative values. Statistical analysis was performed using ANOVA test. Data are expressed as mean ± SD of 3 independent experiments performed in triplicate. Differences were considered statistically significant at P < 0.05. Rosi (Rosiglitazone), Telmi (Telmisartan). ∗Differences between triglyceride levels of treatments with PPAR agonist in relation to control (induction of differentiation with basal medium). # indicates differences found between treatments.

Mentions: The effect of PPARγ agonist was initially studied, whether partial or total, to induce differentiation of ADMSCs into adipocytes. After 10 days of differentiation it was observed that cells were capable of storing triglycerides using both agonists (Figure 1). This observation makes the important role of this nuclear receptor in the process of differentiation of the adipose cells evident. In the present study both total and partial PPARγ agonists induced triglyceride accumulation and differentiation of ADMSCs to mature adipose cells. We have considered the evaluation of a partial agonist of PPARγ because it has been shown that excessive fat accumulation and retention of liquids are some of the undesirable effects of total PPARγ agonists. It is for this reason that selective agonists may have a better therapeutic efficacy [24, 25]. When cells were subjected to a temperature drop, in both cases a reduction in the accumulation of triglycerides was observed (Figures 1(a) and 1(b)). Previous studies in animal models have shown that cold can possibly have a lipolytic effect on fat cells, increasing transporters of fatty acid and specific enzymes such as lipase lipoprotein [26]. It was recently observed that the reduction in temperature can steadily increase expression of higher heat production genes [17]. An important event observed in this study is the increase in markers of energy expenditure triggered by the two types of agonists. Even though it was previously observed that Rosiglitazone may increase PGC-1α and UCP1 levels [27], this is the first evidence of the effect of a PPARγ partial modulator in the activation of these markers (Figure 2). It was additionally observed that temperature reduction may increase the production of markers of energy expenditure, more evident in the case of Rosiglitazone as compared to Telmisartan.


Modifications of Human Subcutaneous ADMSC after PPARγ Activation and Cold Exposition.

Vargas D, Rosales W, Lizcano F - Stem Cells Int (2015)

Effect of cold on triglyceride levels in differentiated human adipocytes. (a) ADMSCs were obtained from human subcutaneous adipocytes differentiated and induced for 10 days with 1 μM of full agonist (Rosiglitazone) and 50 μM partial agonist (Telmisartan). Cells were maintained at 37°C or exposed to 31°C for 4 hours and after, staining was performed with Oil Red O. (b) Quantification of triglyceride levels is expressed as relative values. Statistical analysis was performed using ANOVA test. Data are expressed as mean ± SD of 3 independent experiments performed in triplicate. Differences were considered statistically significant at P < 0.05. Rosi (Rosiglitazone), Telmi (Telmisartan). ∗Differences between triglyceride levels of treatments with PPAR agonist in relation to control (induction of differentiation with basal medium). # indicates differences found between treatments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539182&req=5

fig1: Effect of cold on triglyceride levels in differentiated human adipocytes. (a) ADMSCs were obtained from human subcutaneous adipocytes differentiated and induced for 10 days with 1 μM of full agonist (Rosiglitazone) and 50 μM partial agonist (Telmisartan). Cells were maintained at 37°C or exposed to 31°C for 4 hours and after, staining was performed with Oil Red O. (b) Quantification of triglyceride levels is expressed as relative values. Statistical analysis was performed using ANOVA test. Data are expressed as mean ± SD of 3 independent experiments performed in triplicate. Differences were considered statistically significant at P < 0.05. Rosi (Rosiglitazone), Telmi (Telmisartan). ∗Differences between triglyceride levels of treatments with PPAR agonist in relation to control (induction of differentiation with basal medium). # indicates differences found between treatments.
Mentions: The effect of PPARγ agonist was initially studied, whether partial or total, to induce differentiation of ADMSCs into adipocytes. After 10 days of differentiation it was observed that cells were capable of storing triglycerides using both agonists (Figure 1). This observation makes the important role of this nuclear receptor in the process of differentiation of the adipose cells evident. In the present study both total and partial PPARγ agonists induced triglyceride accumulation and differentiation of ADMSCs to mature adipose cells. We have considered the evaluation of a partial agonist of PPARγ because it has been shown that excessive fat accumulation and retention of liquids are some of the undesirable effects of total PPARγ agonists. It is for this reason that selective agonists may have a better therapeutic efficacy [24, 25]. When cells were subjected to a temperature drop, in both cases a reduction in the accumulation of triglycerides was observed (Figures 1(a) and 1(b)). Previous studies in animal models have shown that cold can possibly have a lipolytic effect on fat cells, increasing transporters of fatty acid and specific enzymes such as lipase lipoprotein [26]. It was recently observed that the reduction in temperature can steadily increase expression of higher heat production genes [17]. An important event observed in this study is the increase in markers of energy expenditure triggered by the two types of agonists. Even though it was previously observed that Rosiglitazone may increase PGC-1α and UCP1 levels [27], this is the first evidence of the effect of a PPARγ partial modulator in the activation of these markers (Figure 2). It was additionally observed that temperature reduction may increase the production of markers of energy expenditure, more evident in the case of Rosiglitazone as compared to Telmisartan.

Bottom Line: In the present study, we determined the effect of partial agonism of PPARγ and temperature reduction on phenotype and metabolic activity of ADMSCs from human adipose subcutaneous tissue.We found that adipocytes differentiated with total and partial agonists of PPARγ and exposed to 31°C are able to respond to cold significantly increasing the expression of thermogenic proteins such as UCP1, PGC1α, and CITED1, a marker of beige phenotype.Additionally, we found that adipocyte cells subjected to cold had a reduction in triglycerides and increased adiponectin levels.

View Article: PubMed Central - PubMed

Affiliation: Centro de Investigación Biomédica, CIBUS, Universidad de La Sabana, Km 7, Autopista Norte de Bogotá, 140013 Chía, Colombia.

ABSTRACT
Mesenchymal stem cells are a diverse population of cells with a wide range of potential therapeutic applications. In particular, cells from adipose tissue have the distinction of being easily accessible and contain a lot of stem cells. ADMSCs can be induced to mature adipocyte and activate the energy expenditure upon treatment with total PPARγ agonists. Additionally these cells may respond to cold by activating the thermogenic program. In the present study, we determined the effect of partial agonism of PPARγ and temperature reduction on phenotype and metabolic activity of ADMSCs from human adipose subcutaneous tissue. We found that adipocytes differentiated with total and partial agonists of PPARγ and exposed to 31°C are able to respond to cold significantly increasing the expression of thermogenic proteins such as UCP1, PGC1α, and CITED1, a marker of beige phenotype. Additionally, we found that adipocyte cells subjected to cold had a reduction in triglycerides and increased adiponectin levels. These data confirm the promising role of ADMSCs as a treatment for metabolic disorders since it is possible to induce them to mature adipocytes and modulate their phenotype toward a cell with high-energy expenditure and metabolic beneficial effect.

No MeSH data available.


Related in: MedlinePlus