Resistin and adiponectin are adipokines with postulated opposite functions. Resistin has been related with insulin resistance in obesity, while adiponectin could be associated to higher insulin ...sensitivity. We have determined whether the production of these two adipokines during the day is related to the feeding rhythm in rats. Resistin mRNA levels in adipose tissue correlated positively with the gastric contents and serum insulin concentration, showing higher levels during the dark phase (period of the highest food intake), especially in the mesenteric depot, while levels decreased during the light phase. The diurnal pattern of resistin expression was not directly reflected in the circulating levels, but it showed a 6-h delay and correlated negatively with the gastric contents and serum insulin. Adiponectin expression followed an opposite pattern, not apparently related to feeding or insulin release, and not translated into changes in circulating levels. Moreover, considering that insulin stimulates resistin expression and that circulating resistin follows a contrary circadian pattern in comparison to insulin, resistin, apart from its role in the increased insulin resistance associated to obesity, could also act as a putative modulator of insulin in the daily feeding/fasting rhythm through a negative feedback regulation of its action.
Aliment Pharmacol Ther 2011; 33: 235–242
Summary
Background Newer therapies are needed for patients with primary biliary cirrhosis and incomplete response to ursodeoxycholic acid (UDCA). Fenofibrate ...is a fibric acid postulated to regulate immune response and cell proliferation.
Aim To evaluate the efficacy and safety of fenofibrate in patients with primary biliary cirrhosis and incomplete response to UDCA.
Methods We undertook a pilot study involving 20 patients with primary biliary cirrhosis and serum alkaline phosphatase (ALP) ≥ 2× ULN. Nonparametric statistical tests and Spearman correlation test were used as appropriate.
Results Twenty patients received fenofibrate (160 mg/day) in addition to UDCA for 48 weeks. Median serum ALP decreased significantly at 48 weeks compared with baseline values 351 (214–779) U/L at baseline vs. 177 (60–384) U/L at 48 weeks, P < 0.05. A rebound in ALP occurred upon drug discontinuation. Serum aspartate aminotransferase and Immunoglobulin M also decreased significantly, while bilirubin and albumin remained unchanged. Median IL‐1 decreased from 28.9 (2.7–10 000) to 11.3 (2.5–277.7) pg/mL (P = 0.049), and median IL‐6 from 4.6 (3.2–5205) to 3.5 (3.2–73.4) pg/mL (P = 0.027). Heartburn was the most frequent adverse event, leading to discontinuation of two study subjects.
Conclusions Combination therapy of fenofibrate and UDCA induced significant biochemical improvement in patients with primary biliary cirrhosis and incomplete response to UDCA. Further studies are warranted.
Summary
What is already known about this subject
The expression of specific genes in peripheral blood cells (PBCs) may be used as biomarkers of the metabolic status.
High levels of expression of ...CPT1A, SLC27A2, INSR, LEPR, FASN and PPARα in PBCs are indicative of a lower risk for the insulin resistant or dyslipidaemic state associated with obesity in children.
Breastfeeding seems to confer protective effects against obesity and its related metabolic problems.
What this study adds
Children who had been breastfed showed higher expression levels of SLC27A2, FASN, PPARα and INSR in PBCs compared with formula‐fed subjects.
The relationship of the PBC transcript levels of SLC27A2, INSR, FASN and PPARα with insulin resistance and dyslipidaemia may be dependent on the type of infant feeding (breast vs. formula).
The transcript levels of the mentioned biomarkers could be useful to distinguish the formula‐fed children who are at higher risk of metabolic alterations.
Background
Blood‐cell transcripts have showed to be good biomarkers of metabolic alterations and their use in early detection and prevention of future disorders is promising.
Objective
This study aimed to examine the relation between previously proposed transcriptional biomarkers of metabolic health (SLC27A2, CPT1A, FASN, PPARα, INSR, LEPR) in peripheral blood cells and the type of infant feeding in a subset of children from the IDEFICS (Identification and Prevention of Dietary‐ and Lifestyle‐Induced Health Effects in Children and Infants) cohort.
Subjects
A total of 237 children aged 2–9 years from eight European countries were studied.
Results
Breastfed children showed higher expression levels of SLC27A2, FASN, PPARα and INSR, and lower risk of being overweight and of having high plasma triglyceride levels vs. formula‐fed children. Besides, overweight formula‐fed children presented higher HOMA‐index than overweight breastfed children (1.90 vs. 1.62); however, this negative effect was absent in formula‐fed children with high expression of SLC27A2. Moreover, formula‐fed children with low expression of SLC27A2, FASN, PPARα and INSR presented higher triglyceride levels than subjects with high expression of these genes (77.7 mg dL−1 vs. 44.8 mg dL−1). This difference was absent in breastfed children.
Conclusions
Protective effects of breastfeeding are reflected in higher expression levels of SLC27A2, FASN, PPARα and INSR in blood cells. These biomarkers may also serve to discriminate the formula‐fed children that are at higher risk of metabolic alterations.
The relationship between interscapular brown adipose tissue (IBAT) thermogenic potential and vitamin A status was investigated by studying the effects of feeding a vitamin A-deficient diet and ...all-trans retinoic acid (tRA) treatment on body weight and IBAT parameters in mice. Feeding a vitamin A-deficient diet tended to trigger opposite effects to those of tRA treatment, namely increased body weight, IBAT weight, adiposity and leptin mRNA expression, and reduced IBAT thermogenic potential in terms of uncoupling protein 1 (UCP1) mRNA and UCP2 mRNA expression. The results emphasize the importance of retinoids as physiological regulators of brown adipose tissue.
Zusammenfassung
Das im Verlauf der letzten Jahrzehnte entstandene Phänomen der sogenannten Adipositaspandemie muss zu großen Teilen den weltweit beobachteten Veränderungen der Lebensumstände und den ...damit einhergehenden veränderten Ernährungs- und Bewegungsgewohnheiten zugeschrieben werden. Die Störung der Energie-Homöostase spielt eine zentrale Rolle bei der Entstehung von Adipositas in weiten Teilen der Weltbevölkerung. Im vorliegenden Übersichtsbeitrag wird der Wissensstand zu zentralen biologischen Mechanismen von Energieaufnahme, Energiespeicherung und Energieverbrauch zusammengefasst. Hierzu gehören zum Beispiel das Hunger-/Sättigungsgefühl, der Lipidumsatz mit den beiden Komponenten der Lipogenese und der Lipolyse, die Adipogenese sowie energieverbrauchende Prozesse wie die (adaptive) Thermogenese und der Grund- und Leistungsumsatz. Anhand von Beispielen soll der mögliche Einfluss genetischer Polymorphismen, die zur Entstehung von Adipositas beitragen können, verdeutlicht werden.
Serum leptin levels and leptin mRNA expression by adipose tissue increase with age and are mainly associated with an increase in adiposity. Regional changes in both leptin production and fat ...distribution contribute to circulating leptin levels and may play a role in the regulation of body weight. a capacity that changes during development. Here, we have studied leptin mRNA expression in four different white adipose tissue depots (epididymal, retroperitoneal, mesenteric, inguinal; namely, EWAT, RWAT, MWAT, IWAT) and in interscapular brown adipose tissue (IBAT). We have also studied their relationship with lipid content and adiposity changes, together with serum leptin levels in male rats at different ages (18, 55, 93, 159, 212, 294 and 355 days). Serum leptin levels increased during development, reaching stable levels at the age of 7 months, and, as expected, were highly correlated with both the adiposity index (r=0.908, P<0.01) and body weight (r=0.906, P<0.01). Leptin mRNA expression also increased with age, following characteristic ontogenic patterns in every adipose tissue depot. The patterns were similar in EWAT and RWAT: leptin expression increased very rapidly during the first 55 days for EWAT and 3 months for RWAT, with a peak in the latter at 7 months, and high expression levels were retained for the rest of the study period. In IWAT and IBAT, leptin expression increased steadily during the 12-month period studied and was significantly lower than levels in EWAT and RWAT. Leptin expression in MWAT increased progressively with age to reach levels close to those of EWAT and RWAT in 10-month-old animals. The pattern of leptin expression in both EWAT and RWAT paralleled their lipid content, and leptin mRNA expression per unit of tissue lipid content was maintained high and constant from a very young age (about 2 and 3 months, respectively). However, the expression of mRNA for leptin (expressed per unit of tissue lipid concentration) in MWAT, IWAT and IBAT increased steadily during the whole period studied, without attaining the maximal levels observed in EWAT and RWAT. MWAT, IWAT and IBAT maintained their capacity to increase leptin mRNA expression in response to an additional accumulation of lipids. Our data demonstrate that there are regional-specific differences and different rates of increase of leptin gene expression within distinct depots of WAT and BAT. These changes cannot be uniquely explained by changes in adiposity or lipid content, implying that there are regional-specific regulatory mechanisms that may depend on the attenuation with age of the beta-adrenergic inhibitory signalling pathway upon leptin expression or on other factors.
The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV ...recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre‐OLT and HBIG regimens post‐OLT. Data from the NIH HBV‐OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1–81) post‐OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log10 copies/mL, 74% were receiving antiviral therapy. Twenty‐five patients experienced virologic breakthrough before OLT. Post‐OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high‐dose, IV low‐dose, intramuscular low‐dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre‐OLT as long as rescue therapy is administered pre‐ and post‐OLT.
In 183 liver transplants for hepatitis B, low dose or finite duration of HBIG when combined with antiviral therapy resulted in low rates of HBV recurrence after liver transplantation, including patients with breakthrough pretransplant, as long as rescue therapy is administered pre‐ and post‐transplant. See Editorial by Gane on page 1721.
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