Hepatic CD36 downregulation parallels steatosis improvement in morbidly obese undergoing bariatric surgery.

BACKGROUND: The notion that hepatic expression of genes involved in lipid metabolism is altered in obese patients is relatively new and its relationship with hepatic steatosis and cardiometabolic alterations remains unclear. OBJECTIVE: We assessed the impact of Roux-en-Y gastric bypass surgery (RYGB) on the expression profile of genes related to metabolic syndrome in liver biopsies from morbidly obese individuals using a custom-made, focused cDNA microarray, and assessed the relationship between the expression profile and hepatic steatosis regression. MATERIALS AND METHODS: Plasma and liver samples were obtained from patients at baseline and 12 months after surgery. Samples were assayed for chemical and gene expression analyses, as appropriate. Gene expression profiles were assessed using custom-made, focused TaqMan low-density array cards. RESULTS: RYGB-induced weight loss produced a favorable reduction in fat deposits, insulin resistance (estimated by homeostasis model assessment of insulin resistance (HOMA-IR)), and plasma and hepatic lipid levels. Compared with the baseline values, the gene expression levels of key targets of lipid metabolism were significantly altered: CD36 was significantly downregulated (-40%; P=0.001), whereas APOB (+27%; P=0.032) and SCARB1 (+37%; P=0.040) were upregulated in response to surgery-induced weight reduction. We also observed a favorable reduction in the expression of the PAI1 gene (-80%; P=0.007) and a significant increase in the expression of the PPARA (+60%; P=0.014) and PPARGC1 genes (+36%; P=0.015). Notably, the relative fold decrease in the expression of the CD36 gene was directly associated with a concomitant reduction in the cholesterol (Spearman's r=0.92; P=0.001) and phospholipid (Spearman's r=0.76; P=0.04) contents in this tissue. CONCLUSIONS: For the first time, RYGB-induced weight loss was shown to promote a favorable downregulation of CD36 expression, which was proportional to a favorable reduction in the hepatic cholesterol and phospholipid contents in our morbidly obese subjects following surgery.

Lipoprotein lipase but not hormone-sensitive lipase activities achieve normality after surgically induced weight loss in morbidly obese patients.

BACKGROUND: Although bariatric surgery is currently the most common practice for inducing weight loss in morbidly obese patients (BMI>40 kg/m2), its effect on the lipid content of adipose tissue and its lipases (lipoprotein lipase [LPL] and hormone-sensitive lipase [HSL]) are controversial. METHODS: We analyzed LPL and HSL activities and lipid content from plasma as well as subcutaneous (SAT) and visceral (VAT) adipose tissue of 34 morbidly obese patients (MO) before and after (6 and 12 months) Roux-en-Y gastric bypass surgery and compare the values with those of normal weight (control) patients. RESULTS: LPL activity was significantly higher in MO (SAT=32.9+/-1.0 vs VAT=36.4+/-3.3 mU/g tissue; p<0.001) than in control subjects (SAT=8.2+/-1.4 vs VAT=6.8+/-1.0 mU/g tissue) in both adipose depots. HSL activity had similar values in both types of tissue (SAT=32.8+/-1.6 and VAT=32.9+/-1.6 mU/g) of MO. In the control group, we found similar results but with lower values (SAT=11.9+/-1.4 vs VAT=12.1+/-1.4 mU/g tissue). Twelve months after surgery, SAT LPL activity diminished (9.8+/-1.4 mU/g tissue, p<0.001 vs morbidly obese), while HSL (46.6+/-3.7 mU/g tissue) remained high. All lipids in tissue and plasma diminished after bariatric surgery except plasma nonesterified fatty acids, which maintained higher levels than controls (16+/-3 vs 9+/-0 mg/dL; p<0.001, respectively). CONCLUSIONS: When obese patients lose weight, they lose not only part of the lipid content of the cells but also the capacity to store triacylglycerides in SAT depots.

Ghrelin and apolipoprotein AIV levels show opposite trends to leptin levels during weight loss in morbidly obese patients.

BACKGROUND: Although bariatric surgery is the most common procedure used to induce weight loss in morbidly obese patients, its effect on plasma satiety factors (leptin, ghrelin, and apolipoprotein (apo)-AIV) is controversial. The aim of this work was to analyze these parameters before and at different times after surgery. METHODS: Plasma was obtained from 34 patients before undergoing Roux-en-Y gastric bypass and during weight loss in the 12 months following surgery. RESULTS: Morbidly obese patients had significantly higher values (147%) of leptin than normal-weight (NW) persons, while their ghrelin levels were 46% less than NW. Apo-AIV levels had approximately the same value in both groups (obese and NW). During weight loss, leptin decreased by 75% and ghrelin increased by 78%. Both parameters reached values less than or near NW, respectively, at 1 year after surgery. During the first month after surgery, apo-AIV plasma levels decreased (47%) but later increased and finally returned to preoperative values. Apo-AIV levels were correlated negatively with leptin and positively with ghrelin. High-density lipoprotein (HDL) levels were positively correlated with those of ghrelin and apo-AIV. CONCLUSIONS: During weight loss, plasma leptin and ghrelin could be good markers of total fat decrease. Ghrelin could also indicate gastric mucous improvement, whereas apo-AIV could indicate the recovery of intestinal function. Changes produced in the HDL levels of morbidly obese patients during weight loss suggest a decreased risk of coronary disease.

Nutritional modulation of protein metabolism after gastrointestinal surgery.

BACKGROUND: The metabolic response to surgery includes alterations in protein metabolism, resulting in a net loss of proteins. Protein hypercatabolism is considered an unavoidable consequence of injury, and an important source of morbidity and mortality. Our purpose was to determine the effect of nutrition on protein metabolism following gastrointestinal surgery, and to elucidate whether postoperative protein loss can be prevented with adequate nutritional support. METHODS: Patients who had undergone gastrointestinal surgery were given four different parenteral nutritions with increasing glucose, lipid and amino acid content during the 7 days following surgery. Nitrogen balance, protein synthesis and protein breakdown were determined using in vivo stable isotope labelling. Other metabolites (3-methylhistidine, creatinine, urea, cortisol, glucose, insulin, amino acids and C-reactive protein) were measured. RESULTS: A nutrition-dependent alteration of protein metabolism was found in response to surgical injury. Nutrition modified nitrogen balance, whole-body protein breakdown and, to a lesser extent, whole-body protein synthesis and muscle protein breakdown. The low-energy parenteral nutrition without amino acids produced a negative nitrogen balance (postoperative day 7=-0.381 g protein kg(-1)day(-1)) and important alterations in postoperative protein metabolism that did not normalize during the study period (day 7 protein synthesis=239% and protein breakdown 217% vs preoperative). Patients receiving the two low energy parenteral nutritions containing amino acids had a less negative nitrogen balance (day 7=-0.011 and -0.133 g protein kg(-1)day(-1)) and a transient increase in protein metabolism. The complete parenteral nutrition maintained, during all studied days, protein metabolism parameters within the preoperative reference range (synthesis day 2=92%, day 4=110% day 7=79%; breakdown day 2=85%, day 4=80%, day 7=76% vs preoperative) and a positive nitrogen balance (day 2=+0.0387, day 4=+0.578 and day 7=+0.227 g protein kg(-1)day(-1)). CONCLUSION: Complete nutritional support can prevent protein loss after gastrointestinal surgery and maintain protein metabolism without alterations.

Usefulness of short-lived proteins as nutritional indicators surgical patients.

BACKGROUND AND AIMS: Biochemical indicators are used to assess the adequacy of nutritional support given to postoperative patients. However, the metabolic alterations present in these patients diminish the efficiency of these indicators. The objective of this work is to determine the usefulness of short-lived proteins as indicators to assess the nutritional support administered to patients during the metabolic stress phase produced by surgery. METHODS: The nitrogen balance and plasma concentrations of transthyretin, retinol binding protein, and insulin-like growth factor-1 were determined in 24 patients who received 4 different nutritional regimens during 7 days after surgery. RESULTS: Transthyretin and retinol binding protein, although sensitive to nutritional intake (P<0.0005 and P<0.04 respectively), were strongly affected by the stress response (P<0.008 and P<0.0003 respectively), thus limiting their usefulness for nutrition assessment. Insulin-like growth factor-1 was not influenced by the stress response and was sensitive to the nutritional supply (P<0.0001). Insulin-like growth factor-1 was the only component that showed similar efficiency than nitrogen balance as nutritional indicator. CONCLUSIONS: Transthyretin and retinol binding protein are not adequate to assess the nutritional supply during the stress phase after surgery, while insulin-like growth factor-1 is a suitable indicator of the adequacy of recent intake in this situation, similar in performance to nitrogen balance.