Moreno-Navarrete, J. (José)
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- FGF15/19 is required for adipose tissue plasticity in response to thermogenic adaptations(2021) Villarroya, F. (Francesc); Berasain, C. (Carmen); Uriarte, I. (Iker); Avila, M.A. (Matías Antonio); Gavaldà-Navarro, A. (Aleix); Moreno-Navarrete, J. (José); Morón-Ros, S. (Samantha); Sabater, M. (Mónica); Giralt, M. (Marta); Fernandez-Real, J.M. (José Manuel)
- Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects(Public Library of Science, 2012) Mayas, D. (Dolores); Gomez-Serrano, M. (María); Tinahones, F.J. (Francisco J.); Frühbeck, G. (Gema); Ricart, W. (Wifredo); Ruiz, B. (Bartomeu); Peral, B. (Belén); Garcia-Santos, E. (Eva); Moreno-Navarrete, J. (José); Ortega, F.J. (Francisco J.); Rodriguez-Hermosa, J.I. (José I.); Fernandez-Real, J.M. (José Manuel)The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects
- Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes(BioMed Central, 2010) Catalan, V. (Victoria); Frühbeck, G. (Gema); Ricart, W. (Wifredo); Moreno-Navarrete, J. (José); Gomez-Ambrosi, J. (Javier); Ortega, F.J. (Francisco J.); Rodriguez-Hermosa, J.I. (José I.); Fernandez-Real, J.M. (José Manuel)Caveolins are 21-24 kDa integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Specific subclasses of caveolae carry out specific functions in cell metabolism. In particular, triglycerides are synthesized at the site of fatty acid entry in one of these caveolae classes. OBJECTIVE AND METHODS: We studied the expression of caveolin-1 (CAV-1) gene in association with metabolic variables in 90 visceral and 55 subcutaneous adipose tissue samples from subjects with a wide range of fat mass, in the stromovascular fraction (SVC) and isolated adipocytes, and during differentiation of human adipocytes. RESULTS: CAV-1 gene expression was significantly decreased in visceral adipose tissue (v-CAV-1) of obese subjects. v-CAV-1 was positively associated with several lipogenic genes such as acetyl-coA carboxylase (ACACA, r = 0.34, p = 0.004) and spot-14 (r = 0.33, p = 0.004). In non-obese subjects v-CAV-1 also correlated with fatty acid synthase (FAS, r = 0.60, p < 0.0001). Subcutaneous (sc) adipose tissue (sc-CAV-1) gene expression was not associated with these lipogenic factors when obese and non-obese subjects were studied together. In obese subjects, however, sc-CAV-1 was associated with fatty acid synthase (FAS, r = 0.36, p = 0.02), sterol regulatory element binding protein-1c (SREBP-1c (r = 0.58, p < 0.0001), ACACA (r = 0.33, p = 0.03), spot-14 (r = 0.36, p = 0.02), PPAR-gamma co-activator-1 (PGC-1, r = 0.88, n = 19). In these obese subjects, sc-CAV-1 was also associated with fasting triglycerides (r = -0.50, p < 0.0001).CAV-1 expression in mature adipocytes was significantly higher than in stromal vascular cells. CAV-1 gene expression in adipocytes from subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue) was significatively associated with fasting triglycerides. CAV-1 gene expression did not change significantly during differentiation of human preadipocytes from lean or obese subjects despite significant increase of FAS gene expression. CONCLUSION: Decreased CAV-1 gene expression was simultaneously linked to increased triglycerides and decreased lipogenic gene expression among obese subjects, paralleling the observations of hypertriglyceridemia in CAV-1 knockout mice. However, the regulation of CAV-1 gene expression seems independent of the adipogenic program.
- Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations(Public Library of Science, 2013) Rubio, A. (Antoni); Serrano, M. (Marta); Fontan, M. (Marina); Puig, J. (Josep); Frühbeck, G. (Gema); Ricart, W. (Wifredo); Casamitjana, R. (Roser); Moreno-Navarrete, J. (José); Salvador, J. (Javier); Ortega, F.J. (Francisco J.); Sabater, M. (Mónica); Fernandez-Real, J.M. (José Manuel); Xifra, G. (Gemma)Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.
- Serum HER-2 concentration is associated with insulin resistance and decreases after weight loss.(BioMed Central, 2010) Martin, A. (Alejandro); Frühbeck, G. (Gema); Ricart, W. (Wifredo); Moreno-Navarrete, J. (José); Menendez, J.A. (Javier A.); Fernandez-Real, J.M. (José Manuel)HER2/neu is a member of the epidermal growth factor receptor family easily detectable in the serum of cancer patients. We aimed to evaluate circulating HER-2 concentrations in association with insulin resistance in healthy and obese subjects. METHODS: Insulin sensitivity (minimal model) and serum HER-2 concentrations were evaluated in a cross sectional study in men (cohort 1, n = 167) and longitudinally after weight loss in obese subjects (cohort 2, n = 30). RESULTS: Serum HER-2 concentrations were positively associated with BMI and waist circumference (both r = 0.18, p = 0.02), post-load glucose (r = 0.28, p = 0.001) and fasting triglycerides (r = 0.26, p = 0.001); and negatively associated with insulin sensitivity (r = -0.29, p = 0.002, n = 109). Subjects with type 2 diabetes showed significantly increased soluble serum HER-2 concentrations. In different multivariate regression models, fasting triglycerides emerged as the factor that independently contributed to 10-11% of serum HER-2 variance.Serum HER-2 concentrations correlated significantly with fasting triglycerides and insulin sensitivity index in subjects from cohort 2. Weight loss led to a significant decrease of serum HER-2 concentrations. The change in serum HER-2 concentrations were significantly associated with the change in percent body fat and fasting triglycerides in young (below the median age of the cohort) subjects. CONCLUSIONS: Serum HER-2 concentrations might be implicated in the pathophysiology of insulin resistance and associated comorbidities.
- The L-[alpha]-lysophosphatidylinositol/GPR55 system and its potential role in human obesity(American Diabetes Association, 2012-02) Vazquez-Martinez, R. (Rafael); Nogueiras, R. (Rubén); Rotellar, F. (Fernando); Diaz-Arteaga, A. (Adenis); Catalan, V. (Victoria); Pulido, M.R. (Marina R.); Frühbeck, G. (Gema); Malagon, M.M. (María M.); Ross, R.A. (Ruth A.); Dieguez, C. (Carlos); Moreno-Navarrete, J. (José); Gomez-Ambrosi, J. (Javier); Imbernon, M. (Mónica); Russel, W.R. (Wendy R.); Whyte, L. (Lauren); Fernandez-Real, J.M. (José Manuel); Guzman, R. (Rocío)GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans.
- Circulating omentin concentration increases after weight loss(BioMed Central, 2010) Catalan, V. (Victoria); Frühbeck, G. (Gema); Ricart, W. (Wifredo); Moreno-Navarrete, J. (José); Gomez-Ambrosi, J. (Javier); Ortega, F.J. (Francisco J.); Fernandez-Real, J.M. (José Manuel)Omentin-1 is a novel adipokine expressed in visceral adipose tissue and negatively associated with insulin resistance and obesity. We aimed to study the effects of weight loss-induced improved insulin sensitivity on circulating omentin concentrations. METHODS: Circulating omentin-1 (ELISA) concentration in association with metabolic variables was measured in 35 obese subjects (18 men, 17 women) before and after hypocaloric weight loss. RESULTS: Baseline circulating omentin-1 concentrations correlated negatively with BMI (r = -0.58, p < 0.001), body weight (r = -0.35, p = 0.045), fat mass (r = -0.67, p < 0.001), circulating leptin (r = -0.7, p < 0.001) and fasting insulin (r = -0.37, p = 0.03). Circulating omentin-1 concentration increased significantly after weight loss (from 44.9 +/- 9.02 to 53.41 +/- 8.8 ng/ml, p < 0.001). This increase in circulating omentin after weight loss was associated with improved insulin sensitivity (negatively associated with HOMA value and fasting insulin, r = -0.42, p = 0.02 and r = -0.45, p = 0.01, respectively) and decreased BMI (r = -0.54, p = 0.001). CONCLUSION: As previously described with adiponectin, circulating omentin-1 concentrations increase after weight loss-induced improvement of insulin sensitivity.