Adipokine response in diabetics and nondiabetics following the Roux-en-Y gastric bypass: a preliminary study

INTRODUCTION: The adipocyte influences eating behavior and metabolism via cytokine secretion. We report our findings of adipokine secretion in a cohort of diabetic and nondiabetic morbidly obese patients before and after Roux-en-Y gastric bypass (RYGB). METHODS: Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: five were diabetic and nine were female. Nonfasting plasma levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha were determined preoperatively and 6 mo postoperatively. C-reactive protein (CRP) was followed as a marker of the metabolic syndrome. RESULTS: The patient age was 42 +/- 11 y, and the preoperative BMI was 50 +/- 6 kg/m(2). The 6 mo BMI fell to 33 +/- 5 kg/m(2) (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In nondiabetic patients, there were significant increases compared with preoperative levels for adiponectin, resistin, and tumor necrosis factor-alpha; leptin was significantly decreased while CRP was unchanged. CRP and leptin levels were both significantly lower (P < 0.05), while all other protein levels were unchanged in diabetic patients. CONCLUSIONS: At 6 mo postoperation, RYGB significantly altered most adipokine levels for nondiabetic patients. Only CRP and leptin were changed in diabetic patients. All patients lost a significant amount of weight over 6 mo, suggesting a different metabolic effect between nondiabetic and diabetic patients after RYGB.     

The EMPOWER Study: Randomized, Prospective, Double-Blind, Multicenter Trial of Vagal Blockade to Induce Weight Loss in Morbid Obesity

Background

Intermittent, reversible intraabdominal vagal blockade (VBLOC? Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia.

Methods

Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n?=?192) or control (n?=?102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12?months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM.

Results

Study subjects consisted of 90?% females, body mass index of 41?±?1?kg/m², and age of 46?±?1?years. Device-related complications occurred in 3?% of subjects. There was no mortality. 12-month percent EWL was 17?±?2?% for the treated and 16?±?2?% for the control group. Weight loss was related linearly to hours of device use; treated and controls with ??12?h/day use achieved 30?±?4 and 22?±?8?% EWL, respectively.

Conclusions

VBLOC? therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.     

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

Background

This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment.

Methods

Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n?=?15) or RYGB (n?=?15).

Results

Mean HbA1c decreased from 9.7 to 6.4 % after RYGB and from 9.1 to 6.1 % in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5?±?0.5) was less than in the IMM group (4.6?±?0.3). After RYGB, FGF19 increased in the fasted (93?±?15 to 152?±?19 pg/ml; P?=?0.008) and postprandial states (area under the curve (AUC), 10.8?±?1.9 to 23.4?±?4.1 pg?×?h/ml?×?10³; P?=?0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC ×10³, 6.63?±?1.3 to 15.16?±?2.56 μM?×?h; P?=?0.003) and decreased after IMM (AUC ×10³, 8.22?±?1.24 to 5.70?±?0.70; P?=?0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r?=?0.54, P?=?0.04) and trended negatively with HbA1c (r?=??0.44; P?=?0.09); these associations were not observed after IMM.

Conclusions

BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

     

Systemic interleukin 1 administration suppresses arachidonic acid-induced ear oedema in the mouse

Recombinant human interleukin 1 beta (IL-1 beta), given intraperitoneally to mice as a single injection, significantly suppressed the development of arachidonic acid (AA)-induced ear oedema. This effect was noted 2 h after administration and for at least 5 days afterwards. IL-1 beta was effective in the dose range of 250 ng-20 micrograms/mouse. Injection of IL-1 beta per se resulted in erythema of the ears, and thus, IL-1 beta has the capacity not only to induce and augment but also to suppress inflammatory responses. Indomethacin administered as subcutaneously-implanted pellets did not influence the IL-1 beta induced-ear erythema, but suppressed to some extent the effect of IL-1 beta on the AA-induced ear oedema.     

Turnover of apoproteins A-I and A-II of high density lipoprotein and the relationship to other lipoproteins in normal and hyperlipidemic individuals

The kinetics of the major apoproteins of high density lipoproteins (HDL), A-I(apoA-I) and A-II(apoA-II), were studied from the specific activity-time curves of these apoproteins, after reinjection of radioiodine-labeled HDL. In all 20 subjects, HDL apoprotein kinetics conformed to a two-pool model. The total fractional removal rates for the two apoproteins were similar, although the irreversible fractional removal rate appeared to be slightly greater for apoA-I. The mean transport for A-I and A-II was 12.2 mg/kg/day and 5.0 mg/kg/day, respectively. The mass of the apoprotein pools was strongly correlated with apoprotein production rate and also, to a lesser degree and inversely, with the irreversible fractional catabolic rate. Transport was directly correlated with body weight. Higher fractional catabolic rates, including the transfer rates between the two pools, were observed in five hypertriglyceridemic subjects; in contrast, five subjects with familial hypercholesterolemia tended to show lower fractional catabolic rates. These findings were supported by (1) a strongly positive correlation between the transport rates of HDL A-I and of very low density lipoprotein (VLDL) apoB, determined simultaneously in 10 subjects; and (2) a significant inverse correlation between the irreversible fractional removal rate of HDLA-I and the concentration of low density lipoprotein (LDL) apoB, measured in 15 subjects. These observations underline the metabolic interrelationships of the major lipoprotein classes. Two subjects with familial hyperalphalipoproteinemia showed enlarged pool sizes, but normal transport, with irreversible fractional removal rates that were in the lower range for the group of 20 subjects.     

Complete nucleotide sequence of the 27-kilobase virulence related locus (vrl) of Dichelobacter nodosus: evidence for extrachromosomal origin

The vrl locus is preferentially associated with virulent isolates of the ovine footrot pathogen, Dichelobacter nodosus. The complete nucleotide sequence of this 27.1-kb region has now been determined. The data reveal that the locus has a G+C content much higher than the rest of the D. nodosus chromosome and contains 22 open reading frames (ORFs) encoding products including a putative adenine-specific methylase, two potential DEAH ATP-dependent helicases, and two products with sequence similarity to a bacteriophage resistance system. These ORFs are all in the same orientation, and most are either overlapping or separated by only a few nucleotides, suggesting that they comprise an operon and are translationally coupled. Expression vector studies have led to the identification of proteins that correspond to many of these ORFs. These data, in combination with evidence of insertion of vrl into the 3' end of an ssrA gene, are consistent with the hypothesis that the vrl locus was derived from the insertion of a bacteriophage or plasmid into the D. nodosus genome.     

Effect of peripheral 2-DG on opioid and neuropeptide Y gene expression

It is well known that 2-Deoxy-d-glucose (2-DG) blocks intracellular utilization of glucose and increases food intake. The aim of the present study was to determine whether administration of 2-DG alters gene expression of the orexigenic peptides, neuropeptide Y (NPY) and endogenous opioids, in the arcuate nucleus of the hypothalamus (ARC). Male Sprague–Dawley rats were injected peripherally (i.p.) with 2-DG (200 or 400 mg/kg body weight) and were sacrificed at 2 or 6 h post injection. Half of the animals were given ad libitum access to food whereas the other half of the animals were food-deprived. 2-DG increased food intake fourfold compared to saline injected animals, but did not affect NPY mRNA levels after 2 h. Messenger RNA levels of ProDynorphin (proDYN), but not pro-opiomelanocortin (POMC) nor proEnkephalin (proENK) were significantly decreased 2 h after 2-DG injection. Administration of 400 mg/kg of 2-DG increased mRNA levels of NPY in the arcuate nucleus after six h, but only in those animals not receiving food.     

The glass ionomer cement: the sources of soluble fluoride

This study aimed to investigate certain processes of fluoride production which enable glass ionomer cements to leach fluoride. Two fluoroaluminosilicate glasses, G338 and LG26 were used. The free and total fluoride which could be dissolved from the glasses was measured, before and after acetic acid washing. Both glasses contained appreciable amounts of soluble fluoride prior to any acid treatment. The latter process reduced the amount to some 75% of the original levels. Replacing the customary polymeric acid with propionic acid produced a cement which disintegrated in water allowing the amount of fluoride generated by the cement forming process to be measured. Cement production increased soluble fluoride by a further 3%. Both glasses behaved similarly when undergoing the various processes. G338 produced significantly greater quantities of fluoride, of the order of 10, compared with LG26 although containing only three times the amount of fluoride in the glass formula. A substantial proportion, over half, of the total fluoride was complexed especially after contact with cement and when G338 was used. During the period of the experiment, 21 days, total fluoride release did not seem to depend on the square root of time.     

Age-related changes in brain proDynorphin gene expression in the rat

Dynorphin has a well-established role in feeding and gustation. Alterations in taste perception and feeding behavior are common with age. We hypothesized that proDynorphin gene expression in brain areas involved in taste and feeding declines with age. Male Sprague-Dawley rats were housed individually with ad libitum access to food and water. Brain punches of the selected regions were dissected out in groups of rats aged 4–6, 12–14 and 18–21 months. ProDynorphin mRNA (measured using a cDNA probe) decreased significantly with age in arcuate nucleus and amygdala; increased significantly with age in hippocampus; and was not significantly affected in nucleus of the solitary tract, cortex, caudate putamen or hypothalamic paraventricular nucleus. These data suggest an age-related decrease in the synthesis of dynorphin in two brain regions strongly associated with feeding behavior, and an increase in dynorphin synthesis in a brain region associated with learning and memory.     

Orexin A decreases lipid peroxidation and apoptosis in a novel hypothalamic cell model

Current data support the idea that hypothalamic neuropeptide orexin A (OxA; hypocretin 1) mediates resistance to high fat diet-induced obesity. We previously demonstrated that OxA elevates spontaneous physical activity (SPA), that rodents with high SPA have higher endogenous orexin sensitivity, and that OxA-induced SPA contributes to obesity resistance in rodents. Recent reports show that OxA can confer neuroprotection against ischemic damage, and may decrease lipid peroxidation. This is noteworthy as independent lines of evidence indicate that diets high in saturated fats can decrease SPA, increase hypothalamic apoptosis, and lead to obesity. Together data suggest OxA may protect against obesity both by inducing SPA and by modulation of anti-apoptotic mechanisms. While OxA effects on SPA are well characterized, little is known about the short- and long-term effects of hypothalamic OxA signaling on intracellular neuronal metabolic status, or the physiological relevance of such signaling to SPA. To address this issue, we evaluated the neuroprotective effects of OxA in a novel immortalized primary embryonic rat hypothalamic cell line. We demonstrate for the first time that OxA increases cell viability during hydrogen peroxide challenge, decreases hydrogen peroxide-induced lipid peroxidative stress, and decreases caspase 3/7 induced apoptosis in an in vitro hypothalamic model. Our data support the hypothesis that OxA may promote obesity resistance both by increasing SPA, and by influencing survival of OxA-responsive hypothalamic neurons. Further identification of the individual mediators of the anti-apoptotic and peroxidative effects of OxA on target neurons could lead to therapies designed to maintain elevated SPA and increase obesity resistance.