Dietary curcumin supplementation promotes browning and energy expenditure in postnatal overfed rats

Background Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following white adipose tissue (WAT) gain throughout life. This research investigated whether curcumin (CUR) supplementation could promote WAT browning and activate thermogenesis in postnatal overfed rats. Methods and results This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), SL rats were fed a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplementation had lower body weight and less WAT gain and had an increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, the increased heat generation were consistent with the expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not in the SL1% CUR rats. In addition, 2% CUR dietary supplementation enhanced the serum norepinephrine levels in SL rats, with upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT. Conclusion Dietary CUR supplementation attenuates body fat gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplementation.

Appetite regulating genes in zebrafish gut; a gene expression study

The underlying molecular pathophysiology of feeding disorders, particularly in peripheral organs, is still largely unknown. A range of molecular factors encoded by appetite-regulating genes are already described to control feeding behaviour in the brain. However, the important role of the gastrointestinal tract in the regulation of appetite and feeding in connection to the brain has gained more attention in the recent years. An example of such inter-organ molecular interaction can be the signals mediated by leptin, a key regulator of body weight, food intake and metabolism, with conserved anorexigenic effects in vertebrates. Leptin signal functions through its receptor ( lepr ) in multiple organs, including the brain and the gastrointestinal tract. So far, the regulatory connections between leptin signal and other appetite-regulating genes remain unclear, particularly in the gastrointestinal system. In this study, we used a zebrafish mutant with impaired function of leptin receptor to explore gut expression patterns of appetite-regulating genes, under different feeding conditions (normal feeding, 7-day fasting, 2 and 6-hours refeeding). We compared these expression patterns to those from wild-type zebrafish, in order to identify leptin-dependent differentially expressed genes located in the zebrafish gut. We provide evidence that most appetite-regulating genes are expressed in the zebrafish gut. On one hand, we did not observed significant differences in the expression of orexigenic genes after changes in the feeding condition, and only one orexigenic gene, hcrt , displayed differential expression under impaired leptin signal. On the other hand, we found 8 anorexigenic genes in wild-types ( cart2 , cart3 , dbi , oxt , nmu , nucb2a , pacap and pomc ), as well as 4 genes in lepr mutants ( cart3 , kiss1, kiss1r and nucb2a ), to be differentially expressed in the zebrafish gut after changes in feeding conditions. Most of these genes also showed significant differences in their expression between wild-type and lepr mutant in at least one of the feeding conditions. Finally, we observed that impaired leptin signalling influences potential regulatory connections between anorexigenic genes in zebrafish gut, particularly connections involving cart2 , cart3 , kiss1 , kiss1r , mchr2 , nmu , nucb2a and oxt . Altogether, these transcriptional changes propose a potential role of the gastrointestinal tract in the regulation of feeding through changes in expression of certain anorexigenic genes in zebrafish.

Crtc1 Deficiency Causes Obesity Potentially via Regulating PPARγ Pathway in White Adipose

Obesity is characterized by excessive fat accumulation and associated with glucose and lipid metabolism disorders. Crtc1, a transcription cofactor regulating CREB activity, has been involved in the pathogenesis of metabolic syndrome; however, the underlying mechanism remains under debate. Here we generated a Crtc1–/– mouse line using the CRISPR/Cas9 system. Under normal feeding conditions, Crtc1–/– mice exhibited an obese phenotype resultant from the abnormal expansion of the white adipocytes. The development of obesity in Crtc1–/– mice is independent of alterations in food intake or energy expenditure. Moreover, Crtc1–/– mice were more prone to insulin resistance and dyslipidemia, as evidenced by higher levels of plasma glucose, insulin and FABP4 than wildtype mice. Transcriptome analysis in liver and epididymal white adipose tissue (eWAT) showed that the fat accumulation caused by Crtc1 deletion was mainly related to lipid metabolism in adipose tissue, but not in liver. GSEA and KEGG analysis identified PPAR pathway to be of the highest impact on lipid metabolism in eWAT. This regulation was independent of a direct interaction between CRTC1 and PPARγ. Our findings demonstrate a crucial role of Crtc1 in regulating lipid metabolism in adipose during development, and provide novel insights into obesity prevention and therapeutics.

ATG5 is instrumental in the transition from autophagy to apoptosis during the degeneration of tick salivary glands

Female tick salivary glands undergo rapid degeneration several days post engorgement. This degeneration may be caused by the increased concentration of ecdysone in the hemolymph during the fast feeding period and both autophagy and apoptosis occur. In this work, we first proved autophagy-related gene (ATG) and caspase gene expression peaks during degeneration of the tick salivary glands. We explored the regulatory role of Rhipicephalus haemaphysaloides autophagy-related 5 (RhATG5) in the degeneration of tick salivary glands. During the fast feeding phase, RhATG5 was cleaved and both calcium concentration and the transcription of Rhcalpains increased in the salivary glands. Recombinant RhATG5 was cleaved by μ-calpain only in the presence of calcium; the mutant RhATG5191-199Δ was not cleaved. Treatment with 20-hydroxyecdysone (20E) led to programmed cell death in the salivary glands of unfed ticks in vitro, RhATG8-phosphatidylethanolamine (PE) was upregulated in ticks treated with low concentration of 20E. Conversely, RhATG8-PE decreased and Rhcaspase-7 increased in ticks treated with a high concentration of 20E and transformed autophagy to apoptosis. High concentrations of 20E led to the cleavage of RhATG5. Calcium concentration and expression of Rhcalpains were also upregulated in the tick salivary glands. RNA interference (RNAi) of RhATG5 in vitro inhibited both autophagy and apoptosis of the tick salivary glands. RNAi of RhATG5 in vivo significantly inhibited the normal feeding process. These results demonstrated that high concentrations of 20E led to the cleavage of RhATG5 by increasing the concentration of calcium and stimulated the transition from autophagy to apoptosis.

Surgical Management of Bilateral Epulides in a Sloth Bear (Melursus ursinus) at Nandankanan Zoological Park

Background: Epulides, tumors of periodontal origin, are commonly reported in dogs and infrequently in cats. But its documentation among wild animals is scarce. Retrospective study of the available literature did not find any report of epulis in sloth bears, though dental pathology is common in captive sloth bears. The present study depicts the details about an incidence of bilateral epulides in a captive sloth bear of Nandankanan Zoological Park, Bhubaneswar, India and its successful surgical management.Methods: A male sloth bear aged about 15 years, developed bilateral swellings at the upper jaw, protruding out of the oral cavity, impeding with its normal feeding and drinking. Close physical examination under general anaesthesia revealed that the swellings are bilateral epulides at the upper jaw involving canines of both sides. The epulides were surgically excised, histopathology of the excised mass was conducted and a course of antibiotic treatment was followed.Result: The epulides were found to be of fibromatous and ossifying type. In the present case, there was no recurrence of epulides at the surgical site after their excision and the procedure proved curative. This work is a complementary contribution to the dental pathology study of sloth bears in captivity.

Toxicological evaluation of transgenic silkworms

Safety of transgenic silkworms must be evaluated before their commercial application. We assessed subacute toxicity using a 28-day feeding study in rats. Eighty rats were evenly allocated into four groups, with each group containing 10 male and 10 female rats. Rats of three groups were fed dried transgenic silkworm H19.9A pupae with overexpressed endogenous Bmhsp19.9, transgenic silkworm A4SOR pupae with overexpressed exogenous SOR, or normal silkworm pupae at a dose of 3.0 g/kg/day, respectively. The fourth group served as a normal feeding control. The body weight, feed consumption, hematology response variables, serum biochemical parameters, organ weights, gross necropsy, and histopathologic of animals were evaluated. No mortality, adverse effects, or major differences in the evaluated parameters were observed in the groups fed transgenic pupae in comparison with the control, suggesting that transgenic silkworms are toxicologically equivalent to normal silkworms and are safe for consumption in rats.

Stearoyl-CoA Desaturase-2 in Murine Development, Metabolism, and Disease

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis. The MUFAs palmitoleoyl-CoA (16:1n7) and oleoyl-CoA (18:1n9) are the major products of SCD2. Palmitoleoyl-CoA and oleoyl-CoA have various roles, from being a source of energy to signaling molecules. Under normal feeding conditions, SCD2 is ubiquitously expressed and is the predominant SCD isoform in the brain. However, obesogenic diets highly induce SCD2 in adipose tissue, lung, and kidney. Here we provide a comprehensive review of SCD2 in mouse development, metabolism, and various diseases, such as obesity, chronic kidney disease, Alzheimer′s disease, multiple sclerosis, and Parkinson′s disease. In addition, we show that bone mineral density is decreased in SCD2KO mice under high-fat feeding conditions and that SCD2 is not required for preadipocyte differentiation or the expression of PPARγ in vivo despite being required in vitro.

Esophagogastric polyurethane bezoar complicated by stomach wall microperforation and acute peritonitis: case report

Background Bezoars are collections of indigestible material in the gastrointestinal tract, mostly described in children. Polyurethane “plastobezoars” consisting of composites used in the construction industry are rarely described bezoars formed in the esophagus and stomach, causing gastrointestinal obstruction, usually necessitating gastrectomy. We describe an unusual presentation of polyurethane bezoar with a volcanic rock consistency, that caused gastrointestinal obstruction and perforation of the stomach wall. Case presentation A 39-year-old man, a construction worker, was referred with signs and symptoms of high gastrointestinal obstruction and abdominal pain. Esophagoscopy revealed a foreign body in the esophagus, 20 cm from the incisor line, causing its obstruction. The attempt to collect the material with forceps failed as the material was too hard. Spiral computed tomography visualized a wide, gas-filled esophagus and a large stomach. The patient with symptoms of acute peritonitis was operated. There were several microperforations of the stomach wall, caused by sharp bezoar fragments that filled the upper one-third of the stomach and lower part of the esophagus. After a longitudinal stomach incision, the bezoar was bluntly dissected from the wall and removed, and the stomach microperforations were closed by wall duplication. After the operation, the patient confessed to drinking, of his own free will, a two-component building foam used to seal pipes. The patient started normal feeding on the 4th day and was discharge home. Conclusions Polyurethane bezoars may cause stomach wall perforation and acute peritonitis. Computed tomography has limited usefulness in patients with polyurethane bezoars due to their low specific weight.

Dietary curcumin supplement promotes browning and energy expenditure in postnatal overfed rats

Background: Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following with white adipose tissue (WAT) gain throughout life. This research was to investigate whether curcumin (CUR) supplement could promote WAT browning and activate thermogenesis in postnatal overfed rats.Methods and results: This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), the SL rats were fed with a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplement had lower body weight and less WAT gain, had increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, increased respiratory exchange ratio (RER) and heat generation were consistent with expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not of the SL1% CUR rats. In addition, 2% CUR dietary supplement enhanced the serum norepinephrine (NE) levels in SL rats, with the upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.Conclusion: Dietary CUR supplement attenuates body weight gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplement.