Limits...
Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss.

Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, Basdevant A, Guerre-Millo M, Poitou C, Zucker JD, Bedossa P, Clément K - Diabetes (2010)

Bottom Line: WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry.The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = -0.30, P = 0.02), and with triglyceride levels (R = -0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05).In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U872, Nutriomique, Paris, France.

ABSTRACT

Objective: Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and omental WAT (oWAT) fibrosis in obesity and its relationship with metabolic alterations and surgery-induced weight loss.

Research design and methods: Surgical biopsies for scWAT and oWAT were obtained in 65 obese (BMI 48.2 ± 0.8 kg/m(2)) and 9 lean subjects (BMI 22.8 ± 0.7 kg/m(2)). Obese subjects who were candidates for bariatric surgery were clinically characterized before, 3, 6, and 12 months after surgery, including fat mass evaluation by dual energy X-ray absorptiometry. WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry.

Results: Fibrosis amount, distribution and collagen types (I, III, and VI) present distinct characteristics in lean and obese subjects and with WAT depots localization (subcutaneous or omental). Obese subjects had more total fibrosis in oWAT and had more pericellular fibrosis around adipocytes than lean subjects in both depots. Macrophages and mastocytes were highly represented in fibrotic bundles in oWAT, whereas scWAT was more frequently characterized by hypocellular fibrosis. The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = -0.30, P = 0.02), and with triglyceride levels (R = -0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05). Importantly, scWAT fibrosis correlated negatively with fat mass loss measured at the three time points after surgery.

Conclusions: Our data suggest differential clinical consequences of fibrosis in human WAT. In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

Show MeSH

Related in: MedlinePlus

Cells associated with WAT fibrosis. A: Hematoxylin eosine staining on subcutaneous (left panel) and omental (right panel) WAT sections. B: Adipocytes and stroma vascular fraction were isolated from 12 subjects. COL1A1, COL3A1, and COL6A1 expression were quantified by real-time PCR. *P < 0.005 (C) scWAT and oWAT biopsies were digested with collagenase. The nondigested fibrosis was collected. Cells that released from the fibrosis were collected and (D) analyzed by immunofluorescence using Pref-1 (red, Cy3-conjugated anti-rabbit IgG), αSMA (green, Cy2-conjugated anti-mouse IgG), FABP4 (red, Cy3-conjugated anti-rabbit IgG), vimentin (green, Cy2-conjugated anti-mouse IgG), and collagen I (red, Cy3-conjugated anti-rabbit IgG). (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2963540&req=5

Figure 2: Cells associated with WAT fibrosis. A: Hematoxylin eosine staining on subcutaneous (left panel) and omental (right panel) WAT sections. B: Adipocytes and stroma vascular fraction were isolated from 12 subjects. COL1A1, COL3A1, and COL6A1 expression were quantified by real-time PCR. *P < 0.005 (C) scWAT and oWAT biopsies were digested with collagenase. The nondigested fibrosis was collected. Cells that released from the fibrosis were collected and (D) analyzed by immunofluorescence using Pref-1 (red, Cy3-conjugated anti-rabbit IgG), αSMA (green, Cy2-conjugated anti-mouse IgG), FABP4 (red, Cy3-conjugated anti-rabbit IgG), vimentin (green, Cy2-conjugated anti-mouse IgG), and collagen I (red, Cy3-conjugated anti-rabbit IgG). (A high-quality digital representation of this figure is available in the online issue.)

Mentions: Paired scWAT and oWAT biopsies were stained by hematoxylin/eosine to detect the presence of cells in fibrosis. Although few nuclei were observed in fibrosis bundles in scWAT (Fig. 2A, left panel), they were abundantly detected in oWAT fibrosis (Fig. 2A, right panel). Thus, fibrosis displays distinct characteristics depending on WAT localization, with more hypocellular fibrosis in scWAT than in oWAT. PCR analysis on paired samples of adipocytes and SVF fractions revealed that expression of three collagens was 4- to 12-fold higher in SVF cells than in adipocytes (Fig. 2B), indicating that the main cellular source of collagens in human WAT is within cells of the stromal vascular fraction.


Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss.

Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, Basdevant A, Guerre-Millo M, Poitou C, Zucker JD, Bedossa P, Clément K - Diabetes (2010)

Cells associated with WAT fibrosis. A: Hematoxylin eosine staining on subcutaneous (left panel) and omental (right panel) WAT sections. B: Adipocytes and stroma vascular fraction were isolated from 12 subjects. COL1A1, COL3A1, and COL6A1 expression were quantified by real-time PCR. *P < 0.005 (C) scWAT and oWAT biopsies were digested with collagenase. The nondigested fibrosis was collected. Cells that released from the fibrosis were collected and (D) analyzed by immunofluorescence using Pref-1 (red, Cy3-conjugated anti-rabbit IgG), αSMA (green, Cy2-conjugated anti-mouse IgG), FABP4 (red, Cy3-conjugated anti-rabbit IgG), vimentin (green, Cy2-conjugated anti-mouse IgG), and collagen I (red, Cy3-conjugated anti-rabbit IgG). (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2963540&req=5

Figure 2: Cells associated with WAT fibrosis. A: Hematoxylin eosine staining on subcutaneous (left panel) and omental (right panel) WAT sections. B: Adipocytes and stroma vascular fraction were isolated from 12 subjects. COL1A1, COL3A1, and COL6A1 expression were quantified by real-time PCR. *P < 0.005 (C) scWAT and oWAT biopsies were digested with collagenase. The nondigested fibrosis was collected. Cells that released from the fibrosis were collected and (D) analyzed by immunofluorescence using Pref-1 (red, Cy3-conjugated anti-rabbit IgG), αSMA (green, Cy2-conjugated anti-mouse IgG), FABP4 (red, Cy3-conjugated anti-rabbit IgG), vimentin (green, Cy2-conjugated anti-mouse IgG), and collagen I (red, Cy3-conjugated anti-rabbit IgG). (A high-quality digital representation of this figure is available in the online issue.)
Mentions: Paired scWAT and oWAT biopsies were stained by hematoxylin/eosine to detect the presence of cells in fibrosis. Although few nuclei were observed in fibrosis bundles in scWAT (Fig. 2A, left panel), they were abundantly detected in oWAT fibrosis (Fig. 2A, right panel). Thus, fibrosis displays distinct characteristics depending on WAT localization, with more hypocellular fibrosis in scWAT than in oWAT. PCR analysis on paired samples of adipocytes and SVF fractions revealed that expression of three collagens was 4- to 12-fold higher in SVF cells than in adipocytes (Fig. 2B), indicating that the main cellular source of collagens in human WAT is within cells of the stromal vascular fraction.

Bottom Line: WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry.The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = -0.30, P = 0.02), and with triglyceride levels (R = -0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05).In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U872, Nutriomique, Paris, France.

ABSTRACT

Objective: Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and omental WAT (oWAT) fibrosis in obesity and its relationship with metabolic alterations and surgery-induced weight loss.

Research design and methods: Surgical biopsies for scWAT and oWAT were obtained in 65 obese (BMI 48.2 ± 0.8 kg/m(2)) and 9 lean subjects (BMI 22.8 ± 0.7 kg/m(2)). Obese subjects who were candidates for bariatric surgery were clinically characterized before, 3, 6, and 12 months after surgery, including fat mass evaluation by dual energy X-ray absorptiometry. WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry.

Results: Fibrosis amount, distribution and collagen types (I, III, and VI) present distinct characteristics in lean and obese subjects and with WAT depots localization (subcutaneous or omental). Obese subjects had more total fibrosis in oWAT and had more pericellular fibrosis around adipocytes than lean subjects in both depots. Macrophages and mastocytes were highly represented in fibrotic bundles in oWAT, whereas scWAT was more frequently characterized by hypocellular fibrosis. The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = -0.30, P = 0.02), and with triglyceride levels (R = -0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05). Importantly, scWAT fibrosis correlated negatively with fat mass loss measured at the three time points after surgery.

Conclusions: Our data suggest differential clinical consequences of fibrosis in human WAT. In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

Show MeSH
Related in: MedlinePlus