Macrophage gene expression in adipose tissue is associated with insulin sensitivity and serum lipid levels independent of obesity.

OBJECTIVE: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. DESIGN AND METHODS: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. RESULTS: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. CONCLUSION: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.

Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.

Obesity and low-grade inflammation: a paediatric perspective.

Childhood obesity is a major public health problem. Low-grade inflammation, a hallmark characterizing adult obesity, may be a pivotal mechanism linking obesity to its numerous systemic complications, with adipose tissue depots secreting and producing inflammatory mediators and visceral fat displaying an increased inflammatory profile. While knowledge is relatively scarce regarding the importance of the adipose tissue inflammation process in children, identifying its contribution in childhood obesity and the associated influences of age, sex, weight status, growth, and adipose depot phenotypes are crucial for understanding physiopathology and implementing early intervention strategies. We review the latest research linking obesity and inflammation in childhood focusing on serum inflammatory markers and the effectiveness of lifestyle interventions in improving systemic inflammation. Generally, there are significant correlations between body mass index and increased c-reactive protein and decreased adiponectin levels in children; these levels tend to be improved in interventions resulting in approximately 5% weight loss, regardless of the type or length of intervention. There is a need for further research measuring other inflammatory mediators (e.g. tumour necrosis factor (TNF)-alpha, IL-6, IL-8) and histological studies examining immune cell infiltration in adipose tissue depots in obese children.

Adipose tissue inflammation and liver pathology in human obesity.

The increase in circulating inflammatory factors found in obese subjects and the recent discovery of macrophage infiltration in white adipose tissue (WAT) have opened up new fields of investigation, allowing a reevaluation of the pathophysiology of human obesity. The so-called 'low-grade' inflammatory state, which characterizes this complex disease, is revealed by the moderate, but chronic, systemic rise of a growing panel of molecules with proinflammatory functions. The qualitative and quantitative alterations in the production of these molecules (free fatty acids, cytokines) by the different WAT cell types, particularly in the omental fat depot, are considered new factors with the potential to modify local WAT biology and to contribute, via the portal system, to liver alteration. The aim of this review is to present the most upto-date knowledge regarding the relationships between inflammatory processes in WAT and non-alcoholic liver disease in human obesity.