Psychological workload and weight gain among women with and without familial obesity

Objective : High job demands and low job influence may be associated with subsequent weight gain. Predisposition to obesity may further modify such associations. The purpose of the study was to determine whether familial predisposition to obesity modified associations between psychological workload and 6‐year weight changes among nurses. Research Methods and Procedures : A total of 6404 Danish nurses 45 to 65 years old, who belonged to the workforce in both 1993 and 1999, answered a questionnaire on psychological workload, body weight, and familial obesity. Women were considered to be predisposed to obesity if they were overweight and had at least one obese parent. Parents’ body shape was reported using pictograms. Results : An increased psychological workload, reflected by high job demands and low influence in job, was associated with an increased body weight. This was particularly the case for nurses being predisposed to obesity, suggesting a synergy between familial obesity predisposition and the psychological workload environment. An interaction test among job demands, familial predisposition to obesity, and weight gain on adjusted data was made. The test showed p = 0.05. The adjusted interaction test among influence in job, familial predisposition to obesity, and weight gain showed p = 0.02. Predisposed nurses who were busy in their job gained 4.4 kg, whereas other nurses gained only 3.2 kg during the 6 years. Similarly, nurses predisposed to obesity with low influence in job had a higher body weight gain (5.4 vs. 3.2 kg) compared with other nurses. Discussion : High psychological workload due to high job demands and low influence in job seems to predict weight gain in general and, in particular, among those nurses with a familial predisposition to obesity.     

Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats

Fibrates are hypolipidemic drugs that activate the peroxisome proliferator-activated receptors. Since fibrates may also increase energy expenditure, we investigated whether fenofibrate (FF) had this effect in diet-induced obese rats. A 2-month administration of a high-fat palatable diet to adult rats increased body weight by 25% and white adipose mass by 163% compared with a standard diet. These effects were prevented by FF, both when administered for the 2 months of high-fat feeding and when given for only the second month. Consequently, FF-treated rats had a final body weight and white adipose tissue mass similar to untreated animals on the standard diet. FF also increased resting metabolic rate, hepatic peroxisomal and mitochondrial palmitoyl-dependent oxygen uptake and mRNA levels of acyl-CoA oxidase and lipoprotein lipase. Finally, FF lowered mRNA levels of uncoupling protein-2 and did not affect mitochondrial respiration in skeletal muscle. Therefore, FF seems to act as a weight-stabilizer mainly through its effect on liver metabolism.     

Moderate red-wine consumption partially prevents body weight gain in rats fed a hyperlipidic diet

Red wine is a beverage that can exert a broad spectrum of health-promoting actions both in humans and laboratory animal models if consumed moderately. However, information about its effect on body weight is scarce. We have evaluated the effect of moderate red wine consumption on body weight and energy intake in male Zucker lean rats fed a hypercaloric diet for 8 weeks. For this purpose, we used three 5-animal groups: a high-fat diet group (HFD), a high-fat-diet red-wine-drinking group (HFRWD), and a standard diet group (SD). After 8 weeks, the HFRWD group had a lower body weight gain (175.66 +/- 2.78% vs 188.22 +/- 4.83%; P<.05) and lower energy intake (269.45 +/- 4.02 KJ/animal.day vs day vs 300.81 +/- 4.52 KJ/animal.day; P<.05) and had less fat mass at epididymal location respect to the whole body weight (0.014 +/- 0.001 vs 0.017 +/- 0.001; P<.05) than the HFD group. However, the red wine didn't modified the fed efficiency 0.012 +/- 0.001 g/KJ for HFRWD group versus 0.013 +/- 0.001 g/KJ for the HFD one (P=.080). These findings, though preliminary, show that moderate red wine intake can prevent the increase of body weight by modulating energy intake in a rat diet-induced model of obesity.     

Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain

The role of serine/threonine protein phosphatase 5 (PP5) in the development of obesity and insulin resistance associated with high-fat diet-feeding (HFD) was examined using PP5-deficient mice (Ppp5c^−/−). Despite similar caloric intake, Ppp5c^−/− mice on HFD gained markedly less weight and did not accumulate visceral fat compared to wild-type littermates (Ppp5c^+/+). On a control diet, Ppp5c^−/− mice had markedly improved glucose control compared to Ppp5c^+/+ mice, an effect diminished by HFD. However, even after 10 weeks of HFD glucose control in Ppp5c^−/− mice was similar to that observed in Ppp5c^+/+ mice on the control diet. Thus, PP5 deficiency confers protection against HFD-induced weight gain in mice.     

Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance.     

Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties

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Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse

A significant change in the Western diet, concurrent with the obesity epidemic, was a substitution of saturated fatty acids with polyunsaturated, specifically linoleic acid (LA). Despite increasing investigation on type as well as amount of fat, it is unclear which fatty acids are most obesogenic. The objective of this study was to determine the obesogenic potency of LA vs. saturated fatty acids and the involvement of hypothalamic inflammation. Forty-eight mice were divided into four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA and protein analysis. All HFD-fed mice were heavier and less glucose tolerant than control. The diet with 22.5% LA caused greater bodyweight gain, decreased activity, and insulin resistance compared to control and 1% LA. All HFDs elevated leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No consistent pattern of inflammatory gene expression was observed, with suppression and augmentation of genes by one or all of the HFDs relative to control. These data indicate that, in male mice, LA induces obesity and insulin resistance and reduces activity more than saturated fat, supporting the hypothesis that increased LA intake may be a contributor to the obesity epidemic.     

Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice

The vgf gene regulates energy homeostasis and the VGF-derived peptide TLQP-21 centrally exerts catabolic effects in mice and hamsters. Here, we investigate the effect of chronic intracerebroventricular (icv) injection of TLQP-21 in mice fed high fat diet (HFD). Fast weight-gaining mice injected with the peptide or cerebrospinal fluid were selected for physiological, endocrine, and molecular analysis. TLQP-21 selectively inhibited the increase in body weight and epididymal white adipose tissue (eWAT) weight induced by HFD in control animals despite both groups having a similar degree of hyperphagia. TLQP-21 normalized the increase in leptin and decrease in ghrelin while increasing epinephrine and epinephrine/norepinephrine ratio when compared to values in controls. Finally, HFD-TLQP-21 mice showed a selective increase of eWAT β3-adrenergic receptor mRNA. Peroxisome-proliferator-activated-receptor-δ and hormone-sensing-lipase mRNA were also upregulated. In conclusion, chronic icv infusion of TLQP-21 prevented the early phase of diet-induced obesity despite overfeeding. These effects were paralleled by activation of catabolic pathways within the eWAT. Our results further support a role for TLQP-21 as a catabolic neuropeptide.     

The Xanthomonas type Ⅲ effector Xop AP prevents stomatal closure by interfering with vacuolar acidification

Plant stomata close rapidly in response to a rise in the plant hormone abscisic acid(ABA) or salicylic acid(SA) and after recognition of pathogenassociated molecular patterns(PAMPs). Stomatal closure is the result of vacuolar convolution, ion efflux, and changes in turgor pressure in guard cells. Phytopathogenic bacteria secrete type Ⅲ effectors(T3Es) that interfere with plant defense mechanisms, causing severe plant disease symptoms. Here, we show that the virulence and infection of Xanthomonas...     

Estrogenic plant extracts reverse weight gain and fat accumulation without causing mammary gland or uterine proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women.     

Lipoic acid prevents body weight gain induced by a high fat diet in rats: Effects on intestinal sugar transport

Several studies have suggested that oxidative stress might cause and aggravate the inflammatory state associated with obesity and could be the link between excessive weight gain and its related disorders such as insulin resistance and cardiovascular diseases. Thus, antioxidant treatment has been proposed as a therapy to prevent and manage obesity and associated complications. Therefore, the aim of the present study was to investigate the effects of supplementation of a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feed efficiency and intestinal sugar absorption, in male Wistar rats. LA supplementation induced a lower body weight gain and adipose tissue size in both control or high fat fed rats accompanied by a reduction in food intake. The group fed on a high fat diet and treated with LA (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF) group (P<0.05), which received the same amount of food than LA-treated animals but with no LA. In fact, LA induced a reduction on feed efficiency and also significantly decreased intestinal α-methylglucoside (α-MG) absorption both in lean and obese rats. These results suggest that the beneficial effects of dietary supplementation with LA on body weight gain are mediated, at least in part, by the reduction observed in food intake and feed efficiency. Furthemore, the inhibitory action of LA on intestinal sugar transport could explain in part the lower feed efficiency observed in LA-treated animals and therefore, highlighting the beneficial effects of LA on obesity.     

SNPs in the coding region of bovine MGAT2 gene are associated with body weight and weight gain

Monoacylglycerol acyltransferase 2 (MGAT2), as a candidate gene for quantitative traits, relates to dietary fat uptake, lipids synthesis and storage, which plays a major role in the absorption of dietary fat by catalyzing the resynthesis of triacylglycerol in enterocytes. In this study, based on DNA pool sequencing and PCR-RFLP methods, polymorphisms of the MGAT2 gene were detected in 1145 Chinese indigenous cattle. The results revealed two novel mutations located on exon 1 and exon 5 (NM_001099136.1:m.84G>T and 756A>G). Hence, we described the HaeIII forced PCR-RFLP method in exon1 and a MluI PCR-RFLP method in exon5 to detect them. In addition, the associations of these polymorphisms with growth traits were evaluated in Nanyang cattle. The results showed that only HaeIII locus was associated with body weight and average daily gain aged 6 months, and individuals with genotype TT showed significantly higher body weight and average daily gain than those with genotype GG.     

Advanced Insulin Management program reduces A1C levels and regimen-related distress without weight gain in patients with type 1 diabetes mellitus

Background: Despite the availability of effective treatments, many patients with diabetes have suboptimal glycemic control.Objective: This study was designed to determine whether the Advanced Insulin Management (AIM) program could help patients with type 1 diabetes mellitus (DM) reduce their A1C levels to ≤7.5% without weight gain, increased incidence of hypoglycemia, or increased diabetes-related distress.Methods: The AIM program, developed to intensify glycemic control in patients with type 1 DM, consisted of a screening visit and 3 to 6 interactive group sessions, depending on whether the patient elects multiple daily injections (MDIs) or an insulin pump. Patients who wanted to learn additional diabetes management skills were referred by their endocrinologist, and those with competent carbohydrate-counting skills and record-keeping practices were eligible to enroll. A nurse, dietitian, psychologist, and physician provided group instruction and supported individual goal setting. The program included depression screening, regimen adjustments, and problem-solving activities. Outcome measures, including blood glucose, A1C, weight, and diabetes-related distress, were tracked for 12 months.Results: The study included 113 adult patients with type 1 DM (59% female; mean age, 39 years). Twenty patients already had insulin pumps, 46 patients initiated pump therapy during the study, and 47 patients elected MDIs. Mean A1C declined by 0.5% (to 7.3%) after 12 months, without weight gain or increased hypoglycemia. A significant decrease in diabetes-related distress was observed.Conclusion: The AIM program was associated with important improvements in glycemic control in patients with type 1 DM, without weight gain or increased hypoglycemic episodes.     

Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without interfering with Ras signal transduction

One virulence strategy used by the opportunistic pathogen Pseudomonas aeruginosa is to target toxic proteins into eukaryotic cells by a type III secretion mechanism. Two of these proteins, ExoS and ExoT, show 75% homology on amino acid level. However, compared with ExoS, ExoT exhibits highly reduced ADP-ribosylating activity and the role of ExoT in pathogenesis is poorly understood. To study the biological effect of ExoT, we used a strategy by which ExoT was delivered into host cells by the heterologous type III secretion system of Yersinia pseudotuberculosis . ExoT was found to induce a rounded cell morphology and to mediate disruption of actin microfilaments, similar to that induced by an ADP-ribosylation defective ExoS (E381A) and the related cytotoxin YopE of Y. pseudotuberculosis . In contrast to ExoS, ExoT had no major effect on cell viability and did not modify or inactivate Ras by ADP-ribosylation in vivo . However, similar to ExoS and YopE, ExoT exhibited GAP (GTPase activating protein) activity on RhoA GTPase in vitro . Interestingly, ExoT(R149K), deficient for GAP activity, still caused a morphological change of HeLa cells. Based on our findings, we suggest that the ADP-ribosylating activity of ExoT target another, as yet unidentified, host protein that is distinct from Ras.     

Pathology of benzalkonium chloride toxicity and its effect on body weight gain in broiler birds

Four groups comprising 16 broiler birds each were given benzalkonium chloride (BC) at 100, 300, 500 and 700 ppm in drinking water for 40 days and one group of 16 birds (control) was kept on plain water. Clinical signs in higher dose groups were respiratory distress, drooling of saliva, difficulty in deglutition, inappetence, apathy, lethargy and loss of body weight. Better body weight gain was recorded in 100 ppm dose rate. At 300 ppm, no significant body weight variation was recorded, whereas, at 500 and 700 ppm dose rates, significantly poor body weight gain was recorded. Major pathological changes were seen in 500 and 700 ppm groups, which exhibited formation of yellow diphtheritic plaques in the buccal cavity, swollen and pale commissures of beak and shortening of tongue. Minute necrotic and ulcerative foci were seen in oesophagus and crop. Hyperplastic and hypertrophic alterations were seen in mucosa of the upper digestive tract. Crop of 300 ppm group revealed formation of well developed epithelial nest with pseudoepitheliomatous hyperplasia at the margin of the lesion. Serum alanine transaminase, urea and uric acid in 500 and 700 ppm groups were elevated whereas no significant variations were observed in the 100 and 300 ppm groups. BC could enhance performance of broiler birds at 100 ppm dose rate. It should not be used beyond 300 ppm.     

1-Aminooxy-3-aminopropane reversibly prevents the proliferation of cultured baby hamster kidney cells by interfering with polyamine synthesis

The effects on cultured baby hamster kidney cells of 1-aminooxy-3-aminopropane, a potent new inhibitor of mammalian ornithine and S-adenosylmethionine decarboxylases and of spermidine synthase, were studied. At 0.5 mM concentration in the culture medium, the drug did not interfere with the transmethylation-transsulfuration pathway nor with the polyamine transport system, but it blocked the proliferation and macromolecule synthesis of the cells and reduced the cellular spermidine level to less than 10% of the control value at identical cell density. These changes were accompanied by a total cessation of the excretion of putrescine, spermidine, and acetylated polyamines into the culture medium, greatly increased activity of ornithine and S-adenosylmethionine decarboxylases, and an accumulation of both decarboxylated and intact S-adenosylmethionine. These effects were reversed by the removal of the inhibitor from the culture medium or by supplementing the medium with either 0.5 mM putrescine or 0.1 mM spermidine. In the former case, however, a lag period of 24 h was necessary for the cells to recover. The elevated concentration of decarboxylated S-adenosylmethionine normalized very slowly but apparently had no harmful effects on the cells. The clonigenic potential of the cells was only slightly reduced by prolonged treatment with 0.5 mM 1-aminooxy-3-aminopropane. Thus, the new drug is not toxic to the cells, but either directly or indirectly stops their proliferation by preventing the adequate formation of putrescine and spermidine.