Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots

Tchkonia, Tamar; Tchoukalova, Yourka D.; Giorgadze, Nino; Pirtskhalava, Tamar; Καραγιαννίδης, Ιορδάνης; Forse, R. Armour; Koo, Ada; Stevenson, Michael; Chinnappan, Dharmaraj; Cartwright, Andrew; Jensen, Michael D.; Kirkland, James L.

doi:10.1152/ajpendo.00265.2004

Cited by 217 publications

(200 citation statements)

References 80 publications

(69 reference statements)

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“…Several studies have reported differences in gene expression (19)(20)(21)(22) and proliferative capacity (23)(24)(25)(26)(27)(28) between fat taken from different depots in rodents and humans, suggesting that genetic programming could affect specific adipose depot development. To address this hypothesis, we performed gene expression analysis of both adipocytes and SVF containing preadipocytes taken from s.c. (flank) fat and intraabdominal (epididymal) fat, using Affymetrix U74Av2 microarrays with 8,017 probe sets representing 6,174 different annotated genes (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Previous work has shown that SVF taken from different adipose depots (23)(24)(25)(26)(27)(28) and from obese versus lean individuals show different propensities to differentiate when placed in tissue culture in vitro (36). In addition, the rate of lipolysis in adipose tissue taken from s.c. sites is lower than that of adipose tissue from visceral or omental sites (37).…”

Section: Discussionmentioning

confidence: 99%

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Evidence for a role of developmental genes in the origin of obesity and body fat distribution

Gesta

Blüher

Yamamoto

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

545

525

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Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte-and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depotspecific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and͞or waist͞hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue.adipose tissue ͉ gene expression ͉ subcutaneous ͉ intraabdominal

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence for a role of developmental genes in the origin of obesity and body fat distribution

Gesta

Blüher

Yamamoto

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

545

525

View full text Add to dashboard Cite

show abstract

“…Several studies are concordant with our findings. Tchkonia et al 24 have shown that adipose tissue contains two different adipocyte populations that are regionally distinct in their replicative capacity and adipogenesis. Interestingly, the subtype with the lower capacities for replication, lipid accumulation and C/EBPa expression was most abundant in the omental preadipocyte population.…”

Section: Discussionmentioning

confidence: 99%

Hypertrophy and hyperplasia of abdominal adipose tissues in women

et al. 2007

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Objective: To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. Research design and methods: We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 4775 years; BMI 27.975.3 kg/m 2 ). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). Results: Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPa, PPARg2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (Pp0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPa, SREBP1c and DGAT2 expression and total body fat mass (r ¼ 0.37, r ¼ 0.41, r ¼ 0.57, respectively, Pp0,05), fat percentage (r ¼ 0.40, r ¼ 0.39, r ¼ 058, respectively, Pp0,05) and subcutaneous adipose tissue area (r ¼ 0.36, r ¼ 0.38, r ¼ 0.58, respectively, Pp0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. Conclusions: These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.

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“…Informed consent was obtained from all human subjects. The preadipocyte isolation procedure and steps taken to ensure culture purity have been described previously (65). To induce senescence, preadipocytes were subjected to 10 Gy of cesium radiation.…”

Section: Methodsmentioning

confidence: 99%

JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age

Tchkonia

Ding

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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569

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Chronic, low grade, sterile inflammation frequently accompanies aging and age-related diseases. Cellular senescence is associated with the production of proinflammatory chemokines, cytokines, and extracellular matrix (ECM) remodeling proteases, which comprise the senescence-associated secretory phenotype (SASP). We found a higher burden of senescent cells in adipose tissue with aging. Senescent human primary preadipocytes as well as human umbilical vein endothelial cells (HUVECs) developed a SASP that could be suppressed by targeting the JAK pathway using RNAi or JAK inhibitors. Conditioned medium (CM) from senescent human preadipocytes induced macrophage migration in vitro and inflammation in healthy adipose tissue and preadipocytes. When the senescent cells from which CM was derived had been treated with JAK inhibitors, the resulting CM was much less proinflammatory. The administration of JAK inhibitor to aged mice for 10 wk alleviated both adipose tissue and systemic inflammation and enhanced physical function. Our findings are consistent with a possible contribution of senescent cells and the SASP to age-related inflammation and frailty. We speculate that SASP inhibition by JAK inhibitors may contribute to alleviating frailty. Targeting the JAK pathway holds promise for treating age-related dysfunction.JAK/STAT pathway | cellular senescence | ruxolitinib | interleukin-6 | frailty

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Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots

Abstract: . Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots.

Cited by 217 publications

References 80 publications

Evidence for a role of developmental genes in the origin of obesity and body fat distribution

Evidence for a role of developmental genes in the origin of obesity and body fat distribution

Hypertrophy and hyperplasia of abdominal adipose tissues in women

JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age

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