Inflammation in subcutaneous adipose tissue: Relationship to adipose cell size

Division of Endocrinology, Stanford University School of Medicine, 300 Pasteur Drive, Rm S025, Stanford, CA 94305-5103, USA.
Diabetologia (Impact Factor: 6.88). 10/2009; 53(2):369-77. DOI: 10.1007/s00125-009-1496-3
Source: PubMed

ABSTRACT Inflammation is associated with increased body mass and purportedly with increased size of adipose cells. We sought to determine whether increased size of adipose cells is associated with localised inflammation in weight-stable, moderately obese humans.
We recruited 49 healthy, moderately obese individuals for quantification of insulin resistance (modified insulin suppression test) and subcutaneous abdominal adipose tissue biopsy. Cell size distribution was analysed with a multisizer device and inflammatory gene expression with real-time PCR. Correlations between inflammatory gene expression and cell size variables, with adjustment for sex and insulin resistance, were calculated.
Adipose cells were bimodally distributed, with 47% in a 'large' cell population and the remainder in a 'small' cell population. The median diameter of the large adipose cells was not associated with expression of inflammatory genes. Rather, the fraction of small adipose cells was consistently associated with inflammatory gene expression, independently of sex, insulin resistance and BMI. This association was more pronounced in insulin-resistant than insulin-sensitive individuals. Insulin resistance also independently predicted expression of inflammatory genes.
This study demonstrates that among moderately obese, weight-stable individuals an increased proportion of small adipose cells is associated with inflammation in subcutaneous adipose tissue, whereas size of mature adipose cells is not. The observed association between small adipose cells and inflammation may reflect impaired adipogenesis and/or terminal differentiation. However, it is unclear whether this is a cause or consequence of inflammation. This question and whether small vs large adipose cells contribute differently to inflammation in adipose tissue are topics for future research. Trial registration: NCT00285844.

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    • "In accordance with this putative regulatory loop, it has been shown that adipogenesis-related genes are downregulated in the adipose tissue of obese and type II diabetic individuals (Yang et al, 2004; Dubois et al, 2006). Furthermore, recent studies have shown that the inflammatory tone associated with obesity leads to the dysregulation of adipogenesis (Gustafson et al, 2009; Isakson et al, 2009; McLaughlin et al, 2009). Here, both specific modulation of gut microbiota and CB 1 receptor blockade decreased plasma LPS levels and increased adipocyte differentiation and lipogenesis. "
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    ABSTRACT: Obesity is characterised by altered gut microbiota, low-grade inflammation and increased endocannabinoid (eCB) system tone; however, a clear connection between gut microbiota and eCB signalling has yet to be confirmed. Here, we report that gut microbiota modulate the intestinal eCB system tone, which in turn regulates gut permeability and plasma lipopolysaccharide (LPS) levels. The impact of the increased plasma LPS levels and eCB system tone found in obesity on adipose tissue metabolism (e.g. differentiation and lipogenesis) remains unknown. By interfering with the eCB system using CB(1) agonist and antagonist in lean and obese mouse models, we found that the eCB system controls gut permeability and adipogenesis. We also show that LPS acts as a master switch to control adipose tissue metabolism both in vivo and ex vivo by blocking cannabinoid-driven adipogenesis. These data indicate that gut microbiota determine adipose tissue physiology through LPS-eCB system regulatory loops and may have critical functions in adipose tissue plasticity during obesity.
    Molecular Systems Biology 07/2010; 6:392. DOI:10.1038/msb.2010.46 · 14.10 Impact Factor
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    Diabetologia 11/2009; 53(2):223-5. DOI:10.1007/s00125-009-1605-3 · 6.88 Impact Factor
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    Archives of Physiology and Biochemistry 09/2010; 117(1):23-43. DOI:10.3109/13813455.2010.513393
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