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BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity.

Kim DH, Do MS - Exp. Mol. Med. (2015)

Bottom Line: Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced.A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice.We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science, Handong Global University, Pohang, Gyungbuk, Korea.

ABSTRACT
Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases.

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Animal model. Seven-week-old male C57BL/6J mice (n=21 per group) were fed a high-fat diet (HFD) (60% fat) for 10 weeks to induce obesity. Body weight and food consumption were monitored once per week. (a) Body weight gain in control/BAFF−/− mice showed a significant difference. (b) Relative weight gain in control/BAFF−/− mice after 10 weeks of HFD feeding expressed as a percent change from initial weight. (c) Food intake in grams. (d) Relative organ weight in grams: (organ weight/body weight) × 100%. Mean values with letters are significantly different (*P<0.05, **P<0.01 and ***P<0.001) by Student's t-test. BAFF, B-cell-activating factor; CON, control; EAT, epididymal adipose tissue; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.
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fig1: Animal model. Seven-week-old male C57BL/6J mice (n=21 per group) were fed a high-fat diet (HFD) (60% fat) for 10 weeks to induce obesity. Body weight and food consumption were monitored once per week. (a) Body weight gain in control/BAFF−/− mice showed a significant difference. (b) Relative weight gain in control/BAFF−/− mice after 10 weeks of HFD feeding expressed as a percent change from initial weight. (c) Food intake in grams. (d) Relative organ weight in grams: (organ weight/body weight) × 100%. Mean values with letters are significantly different (*P<0.05, **P<0.01 and ***P<0.001) by Student's t-test. BAFF, B-cell-activating factor; CON, control; EAT, epididymal adipose tissue; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.

Mentions: Obesity was induced in control and BAFF−/− mice by feeding with an HFD for 10 weeks. BAFF−/− mice responded to HFD feeding with an accelerated body weight gain compared with control mice (Figure 1a). Statistical analysis of weight gain revealed a significant difference between BAFF−/− and control mice from 6 weeks of HFD feeding onward (week 6, P<0.05; week 7, P<0.01; week 8–10, P<0.001). It is noteworthy that the initial body weight of BAFF−/− mice was lower than that of control mice, so the percentage of total weight gain was significantly higher in BAFF−/− mice compared with control mice (Figure 1b). The amount of food intake was not significantly different between the two groups of mice (Figure 1c). Evaluation of body composition between control and BAFF−/− mice revealed that there was an increase in fat mass in the SAT, whereas there was a decrease in the fat mass of the EAT relative to control mice when normalized to body weight (Figure 1d).


BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity.

Kim DH, Do MS - Exp. Mol. Med. (2015)

Animal model. Seven-week-old male C57BL/6J mice (n=21 per group) were fed a high-fat diet (HFD) (60% fat) for 10 weeks to induce obesity. Body weight and food consumption were monitored once per week. (a) Body weight gain in control/BAFF−/− mice showed a significant difference. (b) Relative weight gain in control/BAFF−/− mice after 10 weeks of HFD feeding expressed as a percent change from initial weight. (c) Food intake in grams. (d) Relative organ weight in grams: (organ weight/body weight) × 100%. Mean values with letters are significantly different (*P<0.05, **P<0.01 and ***P<0.001) by Student's t-test. BAFF, B-cell-activating factor; CON, control; EAT, epididymal adipose tissue; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4314587&req=5

fig1: Animal model. Seven-week-old male C57BL/6J mice (n=21 per group) were fed a high-fat diet (HFD) (60% fat) for 10 weeks to induce obesity. Body weight and food consumption were monitored once per week. (a) Body weight gain in control/BAFF−/− mice showed a significant difference. (b) Relative weight gain in control/BAFF−/− mice after 10 weeks of HFD feeding expressed as a percent change from initial weight. (c) Food intake in grams. (d) Relative organ weight in grams: (organ weight/body weight) × 100%. Mean values with letters are significantly different (*P<0.05, **P<0.01 and ***P<0.001) by Student's t-test. BAFF, B-cell-activating factor; CON, control; EAT, epididymal adipose tissue; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.
Mentions: Obesity was induced in control and BAFF−/− mice by feeding with an HFD for 10 weeks. BAFF−/− mice responded to HFD feeding with an accelerated body weight gain compared with control mice (Figure 1a). Statistical analysis of weight gain revealed a significant difference between BAFF−/− and control mice from 6 weeks of HFD feeding onward (week 6, P<0.05; week 7, P<0.01; week 8–10, P<0.001). It is noteworthy that the initial body weight of BAFF−/− mice was lower than that of control mice, so the percentage of total weight gain was significantly higher in BAFF−/− mice compared with control mice (Figure 1b). The amount of food intake was not significantly different between the two groups of mice (Figure 1c). Evaluation of body composition between control and BAFF−/− mice revealed that there was an increase in fat mass in the SAT, whereas there was a decrease in the fat mass of the EAT relative to control mice when normalized to body weight (Figure 1d).

Bottom Line: Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced.A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice.We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science, Handong Global University, Pohang, Gyungbuk, Korea.

ABSTRACT
Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases.

Show MeSH
Related in: MedlinePlus