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Cannabinoid type 1 receptor mediates depot-specific effects on differentiation, inflammation and oxidative metabolism in inguinal and epididymal white adipocytes.

Wagner IV, Perwitz N, Drenckhan M, Lehnert H, Klein J - Nutr Diabetes (2011)

Bottom Line: Uncoupling protein-1 as well as PGC-1α expression was significantly elevated.In conclusion, we found depot-specific effects on differentiation, apoptosis, inflammation and oxidative metabolism in CB1-receptor knockout cells.Thus, CB1-receptor-mediated pathways differentially target adipose tissue depots to a dual effect that minimizes cardiometabolic risk, on the one hand, by diminishing visceral fat, and that enhances thermogenesis in subcutaneous adipocytes, on the other.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine I, University of Luebeck, Luebeck, Germany.

ABSTRACT

Objective: The endocannabinoid system is a major component in the control of energy metabolism. Cannabinoid 1 (CB1)-receptor blockade induces weight loss and reduces the risk to develop the metabolic syndrome with its associated cardiovascular complications. These effects are mediated by central and peripheral pathways. Interestingly, weight loss is mainly achieved by a reduction of visceral fat mass. We analyzed fat depot-specific differences on adipocyte differentiation, inflammation and oxidative metabolism in CB1-receptor knockout cells.

Materials and methods: We used newly generated epididymal/inguinal adipose cell lines from CB1-receptor knockout mice. Differences in differentiation were measured by fat-specific Oil Red O staining and quantitative analysis of key differentiation markers. Induction of apoptosis was evaluated by cell death detection and investigation of p53 phosphorylation. Inflammation markers were quantified by real-time PCR. For analyzing the process of transdifferentiation we measured oxygen consumption and mitochondrial biogenesis.

Results: Differentiation was reduced in visceral adipocytes from CB1-receptor knockout mice as compared with wild-type controls. Moreover, we found an induction of apoptosis in these cells. In contrast, subcutaneous adipocytes from CB1-receptor knockout mice showed an accelerated differentiation and a reduced rate of apoptosis. Inflammation was increased in visceral fat cells, as analyzed by the expression pattern of interleukin-6, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α, whereas in subcutaneous adipocytes these markers were decreased. Furthermore, subcutaneous CB1-receptor knockout cells were more sensitive toward a conversion into a brown fat phenotype. Uncoupling protein-1 as well as PGC-1α expression was significantly elevated. This was accompanied by an increase in mitochondrial biogenesis and oxygen consumption.

Conclusion: In conclusion, we found depot-specific effects on differentiation, apoptosis, inflammation and oxidative metabolism in CB1-receptor knockout cells. Thus, CB1-receptor-mediated pathways differentially target adipose tissue depots to a dual effect that minimizes cardiometabolic risk, on the one hand, by diminishing visceral fat, and that enhances thermogenesis in subcutaneous adipocytes, on the other.

No MeSH data available.


Related in: MedlinePlus

Depot-specific effects on adipocyte differentiation are demonstrated. Oil Red O staining of newly generated inguinal (Ing) and epididymal (Epi) CB1-receptor knockout (KO) cells compared with their wild-type control. Lipid accumulation was visualized at days 0, 3 and 6 during adipogenesis. Microscopic pictures in 40-fold magnification are shown.
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fig1: Depot-specific effects on adipocyte differentiation are demonstrated. Oil Red O staining of newly generated inguinal (Ing) and epididymal (Epi) CB1-receptor knockout (KO) cells compared with their wild-type control. Lipid accumulation was visualized at days 0, 3 and 6 during adipogenesis. Microscopic pictures in 40-fold magnification are shown.

Mentions: In epididymal adipocytes of CB1-receptor knockout, we found a lack of differentiation compared with controls, whereas inguinal CB1-receptor knockout cells demonstrated an accelerated lipid storage compared with inguinal wild-type cells as assessed by microscopic pictures after Oil Red O staining (Figure 1). These observations were confirmed by densitometric analysis of Oil Red O staining (Figures 2a and b). Lipid accumulation in epididymal CB1-receptor knockout cells was significantly reduced on days 3 and 6. In contrast, inguinal CB1-receptor knockout cells showed an increase in differentiation on days 3 and 6. Furthermore, we analyzed main differentiation markers in these cells at days 3 and 6 after induction. The Preadipocyte factor (Pref 1), which is an inhibitory factor of adipogenesis, was markedly induced with a maximum of nearly 700% on day 6 in epididymal CB1-receptor knockout cells, whereas in inguinal cells this marker was significantly reduced by 70%. In line with these results, we found a decrease of PPARγ, Glut 4 and aP2 in epididymal CB1-receptor knockout fat cells by 40%, 68% and 52%, respectively. In inguinal CB1-receptor knockout cells, the expression of these late differentiation markers was elevated (233% PPARγ, 467% aP2, 33% Glut 4) compared with their wild-type controls (Table 1).


Cannabinoid type 1 receptor mediates depot-specific effects on differentiation, inflammation and oxidative metabolism in inguinal and epididymal white adipocytes.

Wagner IV, Perwitz N, Drenckhan M, Lehnert H, Klein J - Nutr Diabetes (2011)

Depot-specific effects on adipocyte differentiation are demonstrated. Oil Red O staining of newly generated inguinal (Ing) and epididymal (Epi) CB1-receptor knockout (KO) cells compared with their wild-type control. Lipid accumulation was visualized at days 0, 3 and 6 during adipogenesis. Microscopic pictures in 40-fold magnification are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3303536&req=5

fig1: Depot-specific effects on adipocyte differentiation are demonstrated. Oil Red O staining of newly generated inguinal (Ing) and epididymal (Epi) CB1-receptor knockout (KO) cells compared with their wild-type control. Lipid accumulation was visualized at days 0, 3 and 6 during adipogenesis. Microscopic pictures in 40-fold magnification are shown.
Mentions: In epididymal adipocytes of CB1-receptor knockout, we found a lack of differentiation compared with controls, whereas inguinal CB1-receptor knockout cells demonstrated an accelerated lipid storage compared with inguinal wild-type cells as assessed by microscopic pictures after Oil Red O staining (Figure 1). These observations were confirmed by densitometric analysis of Oil Red O staining (Figures 2a and b). Lipid accumulation in epididymal CB1-receptor knockout cells was significantly reduced on days 3 and 6. In contrast, inguinal CB1-receptor knockout cells showed an increase in differentiation on days 3 and 6. Furthermore, we analyzed main differentiation markers in these cells at days 3 and 6 after induction. The Preadipocyte factor (Pref 1), which is an inhibitory factor of adipogenesis, was markedly induced with a maximum of nearly 700% on day 6 in epididymal CB1-receptor knockout cells, whereas in inguinal cells this marker was significantly reduced by 70%. In line with these results, we found a decrease of PPARγ, Glut 4 and aP2 in epididymal CB1-receptor knockout fat cells by 40%, 68% and 52%, respectively. In inguinal CB1-receptor knockout cells, the expression of these late differentiation markers was elevated (233% PPARγ, 467% aP2, 33% Glut 4) compared with their wild-type controls (Table 1).

Bottom Line: Uncoupling protein-1 as well as PGC-1α expression was significantly elevated.In conclusion, we found depot-specific effects on differentiation, apoptosis, inflammation and oxidative metabolism in CB1-receptor knockout cells.Thus, CB1-receptor-mediated pathways differentially target adipose tissue depots to a dual effect that minimizes cardiometabolic risk, on the one hand, by diminishing visceral fat, and that enhances thermogenesis in subcutaneous adipocytes, on the other.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine I, University of Luebeck, Luebeck, Germany.

ABSTRACT

Objective: The endocannabinoid system is a major component in the control of energy metabolism. Cannabinoid 1 (CB1)-receptor blockade induces weight loss and reduces the risk to develop the metabolic syndrome with its associated cardiovascular complications. These effects are mediated by central and peripheral pathways. Interestingly, weight loss is mainly achieved by a reduction of visceral fat mass. We analyzed fat depot-specific differences on adipocyte differentiation, inflammation and oxidative metabolism in CB1-receptor knockout cells.

Materials and methods: We used newly generated epididymal/inguinal adipose cell lines from CB1-receptor knockout mice. Differences in differentiation were measured by fat-specific Oil Red O staining and quantitative analysis of key differentiation markers. Induction of apoptosis was evaluated by cell death detection and investigation of p53 phosphorylation. Inflammation markers were quantified by real-time PCR. For analyzing the process of transdifferentiation we measured oxygen consumption and mitochondrial biogenesis.

Results: Differentiation was reduced in visceral adipocytes from CB1-receptor knockout mice as compared with wild-type controls. Moreover, we found an induction of apoptosis in these cells. In contrast, subcutaneous adipocytes from CB1-receptor knockout mice showed an accelerated differentiation and a reduced rate of apoptosis. Inflammation was increased in visceral fat cells, as analyzed by the expression pattern of interleukin-6, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α, whereas in subcutaneous adipocytes these markers were decreased. Furthermore, subcutaneous CB1-receptor knockout cells were more sensitive toward a conversion into a brown fat phenotype. Uncoupling protein-1 as well as PGC-1α expression was significantly elevated. This was accompanied by an increase in mitochondrial biogenesis and oxygen consumption.

Conclusion: In conclusion, we found depot-specific effects on differentiation, apoptosis, inflammation and oxidative metabolism in CB1-receptor knockout cells. Thus, CB1-receptor-mediated pathways differentially target adipose tissue depots to a dual effect that minimizes cardiometabolic risk, on the one hand, by diminishing visceral fat, and that enhances thermogenesis in subcutaneous adipocytes, on the other.

No MeSH data available.


Related in: MedlinePlus