The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance.

The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high-IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP-1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty-acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO-low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high-IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an increase of genes involved in acetyl-CoA and lipoprotein synthesis. This effect is attenuated by metformin. In addition, the expression of most of the genes studied was found to be regulated by insulin.

Effects of obesity/fatty acids on the expression of GPR120.

SCOPE: The effects that fatty acids (FAs) exert on G protein-coupled receptor-120 (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the association between GPR120 and obesity, and the FA effects on its expression. METHODS AND RESULTS: GPR120 levels were analyzed in visceral adipose tissue (VAT) from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a high-fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in the fasting state was lower in morbidly obese subjects (p = 0.04), with a decrease 3 h after a high-fat meal only in morbidly obese subjects (p = 0.043). Also, incubations of visceral adipocytes from these subjects were made with different FAs. In nonobese subjects, palmitic, oleic, linoleic, and docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p < 0.05). In morbidly obese subjects, only linoleic acid produced an increase in GPR120 mRNA and protein levels (p < 0.05). CONCLUSION: Morbidly obese subjects had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after a high-fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120 mRNA and protein levels in visceral adipocytes was lower in morbidly obese subjects.

Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects.

Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

[Development and evolution of laparoscopic adrenalectomy in an specialized team: from the beginning to the outpatient setting]. / Desarrollo y evolución de la suprarrenalectomía laparoscópica en una unidad especializada: de los casos iniciales al hospital de día.

BACKGROUND: After the first reports in 1992, laparoscopic adrenalectomy (LA) has evolved technically until becoming the standard approach for the treatment of most of the adrenal gland diseases. MATERIAL AND METHODS: Retrospective and descriptive study of 67 patients who underwent 68 LA between January-1998 and December-2008 in the Laparoscopic Surgery Unit of the General and Digestive Surgery Service in a third level hospital (only one case of bilateral LA). The group was divided in 2 periods, P-1 (1998-2003, 22 cases) and P-2 (2004-2008, 45 cases), which have been compared to evaluate the evolution of the LA technique. RESULTS: Indications for LA were: 19 incidentalomas, 19 primary hyperaldosteronism, 18 pheocromocitoms, 5 cases of symptomatic and non-functioning adrenal masses, 4 Cushing adenomas and 2 metastases. There was no mortality, only 4 patients had minor complications (6%) and conversion rate was only 3% (2 cases). Mean size of adrenal glands resected was 3.83 cm and the mean operative time was 86 minutes. Mean postoperative hospital stay was 3 days and in P-2 seventeen patients were discharged on an outpatient basis (hospital stay less than 23 hours). CONCLUSIONS: In our experience, LA for the treatment of adrenal diseases has shown to be safe, effective and reproducible with low complications and excellent tolerance by patients. When the learning curve is overcome, hospital stay and operative time clearly decrease. As a consequence, LA can be planned in selected cases as outpatient surgery with good results.

Desarrollo y evolución de la suprarrenalectomía laparoscópica en una unidad especializada: de los casos iniciales al hospital de día / Development and evolution of laparoscopic adrenalectomy in an specialized team: from the beginning to the outpatient setting

Introducción: Desde su descripción inicial en 1992, la suprarrenalectomía laparoscópica (SL) ha evolucionado como técnica hasta convertirse en el abordaje estándar para el tratamiento de la patología quirúrgica adrenal.Material y métodos: Realizamos un estudio observacional descriptivo de 67 pacientes sometidos a 68 SL entre enero de 1998 y diciembre de 2008 en la unidad de cirugía laparoscópica del servicio de cirugía general y digestiva de un hospital de tercer nivel (sólo 1 caso de SL bilateral). Igualmente, la serie se ha dividido en dos periodos: P-1 (1998-2003, 22 casos) y P-2 (2004-2008, 45 casos), que se han comparado para valorar la evolución de la técnica.Resultados: Las indicaciones para la realización de SL fueron: 19 incidentalomas, 19 aldosteronomas, 18 feocromocitomas, 5 casos de masa adrenal no funcionante, 4 adenomas de Cushing y 2 metástasis. La mortalidad fue nula, sólo 4 pacientes presentaron complicaciones menores (6%) y la conversión sólo fue necesaria en 2 casos (3%). El tamaño medio glandular de nuestra serie fue de 3,83 cm y la duración media de la cirugía, 86 min. La estancia hospitalaria media fue de 3 días, y en el P-2 hasta 17 pacientes fueron dados de alta en régimen de cirugía mayor ambulatoria (menos de 23 h de estancia). Conclusiones: En nuestra serie, el abordaje laparoscópico para el tratamiento de la patología quirúrgica suprarrenal se ha demostrado seguro, efectivo, reproducible, con escasas complicaciones y muy bien tolerado por los pacientes. Cuando se supera la curva de aprendizaje, el tiempo quirúrgico y la estancia hospitalaria se reducen, lo cual permite, en casos seleccionados, plantear esta técnica en régimen de cirugía mayor ambulatoria (AU)

Background: After the first reports in 1992, laparoscopic adrenalectomy (LA) has evolved technically until becoming the standard approach for the treatment of most of the adrenal gland diseases.Material y methods: Retrospective and descriptive study of 67 patients who underwent 68 LA between January-1998 and December-2008 in the Laparoscopic Surgery Unit of the General and Digestive Surgery Service in a third level hospital (only one case of bilateral LA). The group was divided in 2 periods, P-1 (1998-2003, 22 cases) and P-2 (2004-2008, 45 cases), which have been compared to evaluate the evolution of the LA technique.Results: Indications for LA were: 19 incidentalomas, 19 primary hyperaldosteronism, 18 pheocromocitoms, 5 cases of symptomatic and non-functioning adrenal masses, 4 Cushing adenomas and 2 metastases. There was no mortality, only 4 patients had minor complications (6%) and conversion rate was only 3% (2 cases). Mean size of adrenal glands resected was 3,83 cm and the mean operative time was 86 minutes. Mean postoperative hospital stay was 3 days and in P-2 seventeen patients were discharged on an outpatient basis (hospital stay less than 23 hours).Conclusions: in our experience, LA for the treatment of adrenal diseases has shown to be safe, effective and reproducible with low complications and excellent tolerance by patients. When the learning curve is overcome, hospital stay and operative time clearly decrease. As a consequence, LA can be planned in selected cases as outpatient surgery with good results (AU)

Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test.

Recent studies suggest that measuring the free-fatty acids (FFA) during an intravenous glucose tolerance test (IVGTT) may provide information about the metabolic associations between serum FFA and carbohydrate and insulin metabolism. We evaluated the FFA profile during an IVGTT and determined whether this test changes the composition and concentration of FFA. An IVGTT was given to 38 severely obese persons before and 7 months after undergoing bariatric surgery and also to 12 healthy, nonobese persons. The concentration and composition of the FFA were studied at different times during the test. The concentration of FFA fell significantly faster during the IVGTT in the controls and in the severely obese persons with normal-fasting glucose (NFG) than in the severely obese persons with impaired-fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) (P < 0.05). Significant differences were found in the time to minimum serum concentrations of FFA (control = NFG < IFG < T2DM) (P < 0.001). These variables improved after bariatric surgery in the three groups. The percentage of monounsaturated and n-6 polyunsaturated FFA in the control subjects and in the obese persons, both before and after surgery, decreased significantly during the IVGTT. In conclusion, during an IVGTT, severely obese persons with IFG or T2DM experienced a lower fall in the FFA than the severely obese persons with NFG and the controls, becoming normal after bariatric surgery.

Plasma visfatin concentrations in severely obese subjects are increased after intestinal bypass.

OBJECTIVE: Visfatin has shown to be increased in obesity and in type 2 diabetes. The aim of this study was to determine the change in plasma visfatin in severely obese (SO) persons after weight loss following bariatric surgery in relation to glucose concentration. RESEARCH METHODS AND PROCEDURES: Visfatin and leptin were studied in 53 SO persons (BMI, 54.4 +/- 6.8 kg/m(2)) before and 7 months after bariatric surgery and in 28 healthy persons (BMI, 26.8 +/- 3.8 kg/m(2)). All of the patients underwent bariatric surgery with biliopancreatic diversion or gastric bypass. RESULTS: The pre-surgery levels of visfatin in the SO group were greater than in the control group (55.9 +/- 39.9 vs. 42.9 +/- 16.6 ng/mL, p = 0.024). This increase was significant in the SO group with impaired fasting glucose (63.4 +/- 36.6 ng/mL) and diabetes (60.0 +/- 46.0 ng/mL). SO patients with normal fasting glucose had similar levels of visfatin to the controls. Seven months after surgery, visfatin levels were significantly increased (84.8 +/- 32.8 ng/mL, p < 0.001). This increase was independent of the pre-surgical glucose levels. The type of bariatric surgery had no influence on visfatin levels. Post-surgical visfatin was significantly correlated with the post-surgery plasma concentrations of leptin (r = 0.39, p = 0.014). DISCUSSION: Plasma levels of visfatin in the SO group were increased but only when accompanied by high glucose levels, even in the range of impaired fasting glucose. Bariatric surgery causes an increase in visfatin, which is correlated mainly with the changes produced in the leptin concentration.