In Vitro Synthesis of Triglycerides and Cholesterol in Human Gallbladder Mucosa

Triglyceride and sterol synthesis was investigated in vitro in the gallbladder mucosa from control subjects and patients with acalculous cholesterolosis. The incorporation rate of ¹⁴C-acetate was 1.6 ± 0.2 nmol/g/h into cholesterol (sum of squalene, methyl sterols, and cholesterol) and 5.7 ± 0.8 nmol/g/h into triglycerides. The rates were significantly correlated with each other (r = 0.667). The conversion of ³H-mevalonate into cholesterol (49 ± 10 nmol/g/h) and triglycerides (4.7 ± 1.2 nmol/g/h) indicated a high activity in the postmevalonate cholesterol synthesis and an active shunt pathway of mevalonate metabolism. The synthesis rates of cholesterol, triglycerides, and sterol esters were closely interrelated, were unaltered in cholesterolosis, and were not correlated with the serum, biliary, and mucosal lipid concentrations. Thus, despite marked lipid accumulation the lipid synthesis proceeds effectively in the gallbladder mucosa with cholesterolosis.     

An evaluation of the association between fibromyalgia and repetitive strain injuries in metalworkers of an industry in Guarulhos, Brazil

Repetitive strain injuries are a common diagnostic label for musculoskeletal pain occurring at the workplace. Although many individuals present with diffuse pain, the diagnosis of fibromyalgia in this setting is rare. Our objective was to establish the point prevalence of the fibromyalgia syndrome in a population of assembly line workers in S?o Paulo, Brazil. METHODS: Thirty-four workers with repetitive strain injury diagnoses were studied and compared with 49 workers, paired by age, sex, and labor function. All individuals were studied by a comprehensive clinical protocol. Diagnosis of fibromyalgia syndrome was established when the 1990 American College of Rheumatology criteria for this syndrome were met. RESULTS: Among the 34 workers with the diagnosis of repetitive strain injuries, 58.8% fulfilled the American College of Rheumatology criteria for fibromyalgia syndrome, while only 10.4% of the controls met the same criteria. CONCLUSIONS: Fibromyalgia syndrome was largely involved in the symptoms of patients with repetitive strain injuries, as opposed to coworkers with non-repetitive strain injuries. So, instead of the repetitive strain injuries label, many of these cases should be called fibromyalgic patients.     

Vitamin B12 and folic acid plasma levels after ileocecal and ileal neobladder reconstruction

Objectives

To compare the plasma levels of vitamin B₁₂ and folic acid following resection of ileocecal or ileal segments used for orthotopic bladder substitution.

Methods

Hemoglobin, hematocrit, and plasma levels of vitamin B₁₂ and folic acid were measured in 34 patients with ileocecourethrostomy (ICUS) and in 16 patients with ileal reservoir (IR), with a mean follow-up of 59.8 ± 41.9 months. The results were compared with regard to both the type of operation and the length of time since surgery.

Results

The level of folic acid was normal in all patients. The mean level of vitamin B₁₂ in the ICUS group was 413.67 ± 160.45 ng/mL compared to 257.63 ± 121.36 for the IR group. This difference was statistically significant. In the IR group, 18.75% of the patients had a level of vitamin B₁₂ below normal.

Conclusions

There is a tendency for vitamin B₁₂ levels to fall in patients in whom the ileum is used. Resection of the ileocecal segment including the junction does not alter the level of vitamin B₁₂.     

Alexithymia affects patients with hidradenitis suppurativa

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that impairs patients’ quality of life. Various psychiatric or psychological conditions have been associated with HS, however, no data are available on alexithymia, a psychological construct characterized by the inability to express, describe, and recognize feelings.

Objectives

To assess the presence of alexithymia in HS patients.

Materials & Methods

Demographic and clinical data from patients with HS were collected. Alexithymiawas assessed using the Toronto Alexithymia Scale (TAS)-20 questionnaire to define non-alexithymic subjects (scoring 20-50), borderline (possible) alexithymia subjects (scoring 51-60), and alexithymic subjects (scoring≥61). The alexithymic personality trait is identified based on TAS-20 score≥51.

Results

This multicentre study included 86 HS patients, 100 obese individuals, and 85 healthy control subjects. The mean TAS-20 score was significantly higher in the HS patient cohort (55.37 ±13.42) than in the control group (40.96±10.47) (p<0.001). Compared to the healthy and obese control groups, the prevalence of alexithymic personality trait in HS patients was 61.6% versus 21.95% and 32%, respectively (p<0.001). Of the HS patients, 37.2% were classified as alexithymic and 24.4% as borderline alexithymia.

Conclusions

This is the first study in which an association between HS and alexithymia has been reported, expanding the spectrum of psychological disorders associated with HS.

     

Glucagon‐like peptide‐1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high‐fat diet in nonalcoholic steatohepatitis

Background/Aims: High‐fat dietary intake and low physical activity lead to insulin resistance, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Recent studies have shown an effect of glucagon‐like peptide‐1 (GLP‐1) on hepatic glucose metabolism, although GLP‐1 receptors (GLP‐1r) have not been found in human livers. The aim of this study was to investigate the presence of hepatic GLP‐1r and the effect of exenatide, a GLP‐1 analogue, on hepatic signalling. Methods: The expression of GLP‐1r was evaluated in human liver biopsies and in the livers of high‐fat diet‐treated rats. The effect of exenatide (100 nM) was evaluated in hepatic cells of rats fed 3 months with the high‐fat diet. Results: GLP‐1r is expressed in human hepatocytes, although reduced in patients with NASH. Similarly, in rats with NASH resulted from 3 months of the high‐fat diet, we found a decreased expression of GLP‐1r and peroxisome proliferator‐activated receptor γ (PPARγ), and reduced peroxisome proliferator‐activated receptor α (PPARα) activity. Incubation of hepatocytes with exenatide increased PPARγ expression, which also exerted an insulin‐sensitizing action by reducing JNK phosphorylation. Moreover, exenatide increased protein kinase A (PKA) activity, Akt and AMPK phosphorylation and determined a PKA‐dependent increase of PPARα activity. Conclusions: GLP‐1 has a direct effect on hepatocytes, by activating genes involved in fatty acid β‐oxidation and insulin sensitivity. GLP‐1 analogues could be a promising treatment approach to improve hepatic insulin resistance in patients with NAFLD/NASH.     

Effect of Oral Sebacic Acid on Postprandial Glycemia, Insulinemia, and Glucose Rate of Appearance in Type 2 Diabetes

OBJECTIVE

Dicarboxylic acids are natural products with the potential of being an alternate dietary source of energy. We aimed to evaluate the effect of sebacic acid (a 10-carbon dicarboxylic acid; C10) ingestion on postprandial glycemia and glucose rate of appearance (R_a) in healthy and type 2 diabetic subjects. Furthermore, the effect of C10 on insulin-mediated glucose uptake and on GLUT4 expression was assessed in L6 muscle cells in vitro.

RESEARCH DESIGN AND METHODS

Subjects ingested a mixed meal (50% carbohydrates, 15% proteins, and 35% lipids) containing 0 g (control) or 10 g C10 in addition to the meal or 23 g C10 as a substitute of fats.

RESULTS

In type 2 diabetic subjects, the incremental glucose area under the curve (AUC) decreased by 42% (P < 0.05) and 70% (P < 0.05) in the 10 g C10 and 23 g C10 groups, respectively. At the largest amounts used, C10 reduced the glucose AUC in healthy volunteers also. When fats were substituted with 23 g C10, AUC of R_a was significantly reduced on the order of 18% (P < 0.05) in both healthy and diabetic subjects. The insulin-dependent glucose uptake by L6 cells was increased in the presence of C10 (38.7 ± 10.3 vs. 11.4 ± 5.4%; P = 0.026). This increase was associated with a 1.7-fold raise of GLUT4.

CONCLUSIONS

Sebacic acid significantly reduced hyperglycemia after a meal in type 2 diabetic subjects. This beneficial effect was associated with a reduction in glucose R_a, probably due to lowered hepatic glucose output and increased peripheral glucose disposal.The World Health Report launched in 2002 by the World Health Organization advised that more than 1 billion adults worldwide are overweight and at least 300 million are clinically obese. Type 2 diabetes can be considered a threatening obesity-related disease because hyperglycemia causes relevant complications such as micro- and macroangiopathy. Patients with type 2 diabetes exhibit increased hepatic glucose output, which is identified as the main cause of fasting hyperglycemia and is associated with impaired plasma glucose clearance (1) and reduced hepatic synthesis of glycogen of ∼25–45% compared with that in nondiabetic subjects (2). Increased hepatic gluconeogenesis has been considered to be responsible for elevated hepatic glucose output in type 2 diabetes (3). When glycogen is available in adequate amounts, there is an autolimitation of hepatic glucose production. In diabetes, a breakdown of this autoregulation may occur if glycogenolysis is limited by glycogen depletion (4).Jenkins et al. (5) have shown that spreading the nutrient load over a longer period of time by increased meal frequency, the so-called nibbling diet, is beneficial in terms of reduction of circulating levels of glucose, insulin, and free fatty acids in type 2 diabetes. Thus, the availability of snacks poor in fat and that do not induce hyperglycemia and/or overstimulate insulin secretion would be a good tool in the diet of insulin-resistant, type 2 diabetic subjects.Dicarboxylic acids are naturally occurring substances produced by both higher plants and animals via ω-oxidation of fatty acids (6,7). In plants, long-chain dicarboxylic acids are components of natural protective polymers, cutin and suberin, which support biopolyesters involved in waterproofing the leaves and fruits, regulating the flow of nutrients among various plant cells and organs, and minimizing the deleterious impact of pathogens (7). In animals and humans, medium chain dicarboxylic acids, which include prevalently sebacic (C10) and dodecanedioic (C12) acids, derive from the β-oxidation of longer chain dicarboxylic acids (8). Long-chain dicarboxylic acids, in turn, are formed from the correspondent fatty acids by ω-oxidation in the microsomal membranes (9) or are taken in with a diet rich in vegetables (7).We have shown previously that medium-chain dicarboxylic acids represent a suitable alternate energy substrate to glucose in clinical conditions with marked insulin resistance and/or impaired aerobic glycolysis (10). Interestingly, in type 2 diabetes, medium-chain dicarboxylic acids are rapidly oxidized, do not stimulate insulin secretion, and reduce muscle fatigue (11). Nevertheless, the effect of C10 or C12, not as a substitute but in addition to available carbohydrates, on glucose homeostasis has never been studied.On this basis, our aim was to investigate the effect of oral administration of C10 on postprandial glycemia, insulinemia, and glucose rate of appearance (R_a) in type 2 diabetic subjects compared with that in healthy volunteers. To further elucidate the mechanism of action of sebacic acid in diabetes, insulin-mediated glucose uptake and GLUT4 protein expression were assessed in L6 cells in vitro.