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Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss.

Background/objective: White-to-brown adipose tissue remodeling (browning) in response to different stimuli constitutes an active research area for obesity treatment. The emergence in traditional white adipose tissue (WAT) depots of multilocular adipocytes that express uncoupling protein 1 (UCP1) and resemble brown adipocytes, the so called 'brite' adipocytes, could contribute to increased energy expenditure. In rodents, obesogenic stimuli such as the intake of hyperlipidic diets can increase brown adipose tissue (BAT) thermogenic capacity and contribute to maintaining body weight. The aim of this study was to investigate the potential of two different hyperlipidic diets, a commercial high-fat (HF) diet and a highly palatable cafeteria (CAF) diet, to induce WAT browning., Methods: We analyzed gene expression of a wide number of brown/brite adipocyte markers in different WAT depots, in BAT and in peripheral blood mononuclear cells (PBMCs) increasingly being used in nutrition studies as a potential source of biomarkers of physiological effects. We also performed morphological analysis of adipose tissue., Results: Both HF diets studied were able to increase the expression of the markers studied in WAT in a depot-specific manner, as well as in BAT; some of these changes were also reflected in PBMCs. This increased browning capacity was translated into the appearance of UCP1- and CIDE-A (cell death-inducing DFFA-like effector A)-positive brite adipocytes in retroperitoneal WAT. Administration of the CAF diet, associated with higher adiposity, produced the strongest impact on the parameters studied while its withdrawal restored basal conditions., Conclusions: Acquisition of brown adipocyte features in WAT could evidence an adaptation to try to counteract increased adiposity due to the intake of HF diets. Additionally, PBMCs could constitute an interesting easily obtainable material to assess the effect of nutritional interventions on browning capacity.

We have investigated the effects of long term intake of two unbalanced diets (rich in fat -HF- or protein -HP-) administered under isocaloric conditions to a control balanced diet (pair-feeding) to adult rats. Isocaloric intake of a HF diet did not affect the body weight but increased adiposity, liver-fat deposition, and induced insulin resistance. Gene expression changes in the liver and adipose tissue (increased lipolytic and decreased lipogenic gene expression) could try to compensate for increased adiposity. The HP diet decreased caloric intake, the body weight, the size of subcutaneous adipocytes, and circulating cholesterol. Higher insulin levels apparently not related to insulin resistance were observed. Changes at the gene expression level reflected an adaptation to lower diet carbohydrate content and to the use of amino acids as the energy source. The kidney size increased in HP-fed animals but serum creatinine was not affected. Circulating TNF-alpha levels were higher in both dietary models. Thus, a long-term increase in dietary fat proportion produces alterations related to metabolic syndrome even in the absence of increased body weight, whereas an increase in diet protein content reduces the body weight but alters metabolic parameters and kidney size which could be linked to an increased risk of suffering from different pathologies.

Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice. No studies have been reported thus far in human adipose tissue or human adipocytes. We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models. Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPARγ and IRS1) in both visceral and subcutaneous human adipose tissue. BMI increase was the main contributor to adipose RB1 downregulation. In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss. RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation. In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype. In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes. Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes.