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To determine whether pericruciate fat pad (PCFP) signal intensity alteration and maximal area are associated with incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Participants were from the Osteoarthritis Initiative (OAI) study. Case knees (n = 355) were defined by incident ROA between 12 and 48 months visits and were matched by sex, age, and radiographic status with control knees (n = 355). Magnetic resonance images (MRIs) were used to assess PCFP signal intensity alteration and PCFP maximal area at P0 (time of onset of ROA), P-1 (1 year prior to P0), and baseline. Conditional logistic regression analyses were applied to assess associations between PCFP measures and the risk of incident ROA. The mean age of participants was 60.1 years and 66.9% were women. In multivariable analyses, PCFP signal intensity alteration measured at three time points (OR [95%CI]: 1.28 [1.10–1.50], 1.52 [1.30–1.78], 1.50 [1.27–1.76], respectively) and PCFP maximal area (OR [95%CI]: 1.21 [1.03–1.42], 1.27 [1.07–1.52], 1.37 [1.15–1.62], respectively) were significantly associated with incident ROA. PCFP signal intensity alteration and maximal area were associated with incident ROA over 4 years, implying that they may have roles to play in ROA. • Pericruciate fat pad signal intensity alteration and maximal area were associated with incident ROA, implying that they may have roles to play in ROA.

Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues.Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/ db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood.Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11).Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

Aim. To reveal the characteristic features of tumor growth after orthotopic (OT) and intraperitoneal transplantation (IT) of high-grade syngeneic ovarian carcinoma. Material and methods. Twenty mature female Wistar rats were randomized into two groups of ten each. The first group – animals underwent OT of ovarian carcinoma (4,3×106 cells) under the membrane of the bursa of the left and right ovaries; the second group – animals underwent IT of the tumor (4,3×107 cells). The endpoints of the study included an assessment of the overall survival (OS) of rats in two groups, determination of the peritoneal cancer index (PCI) on autopsy, and ascites weight. Autopsy material was histologically assessed analysis by light microscopy after standard staining. Cytological examination of ascitic fluid was carried out. Results. Median OS was 29 days and 21 days in the OT and IT groups, respectively (log-rank test, P = 0.0276). Autopsy did not reveal significant differences in total PCI (12.6 vs 13.6 in the OT and IT groups, respectively) and ascites weight (78.0 g in the OT vs 65.8 g in the IT group). The method of transplantation did not affect the tumor grafting, histological characteristics, the nature of intraperitoneal spread and the ascites volume. It should be noted that there was a greater volume of tumor lesions in the organs of the reproductive system of rats (ovaries, uterus with horns, paragonadal fat pad) in the OT group. Conclusion. Both methods of transplantation allow to reproduce the advanced stages (III-IV stages) of epithelial ovarian carcinoma in women. OT requires more time and operating conditions. OT and IT can be used to solve various problems in fundamental and routine preclinical cancer research.

BACKGROUND Androgens control rodent inguinoscrotal testicular descent during a "programming window" (E12-17). It is proposed that androgen masculinises the genitofemoral nerve, but the mechanism remains unknown. We investigate androgen receptor (AR)-containing target organs: inguinal fat pad (IFP) and mammary bud (MB), supplied by the genitofemoral nerve, hypothesizing that neurotrophic factors may retrogradely masculinise the GFN. METHODS The IFP, MB and bulbocavernosus (BC) muscle were collected at E12.5/E17.5 from androgen receptor knockout (ARKO) mice and wild-type (WT) littermates. Immunofluorescence and gene expression (RT-qPCR; n = 8/group) for Bdnf, active (TrkB) and inactive (truncated TrkB) receptors, Cntf and Cntf receptor were performed. RESULTS In the IFP at E12.5, ARKO TrkB mRNA expression was significantly downregulated compared to WT males (p

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting not only the synovial joints but also multiple extra-articular sites, including ankle and foot soft tissue. Hindfoot abnormalities usually follow those in the forefoot, with up to 4 out of 10 patients experiencing talalgia during their disease course. Enthesophytosis, retrocalcaneal bursitis, and plantar fasciitis are among the most common etiologies, while heel fat pad abnormalities like subcalcaneal bursitis are rare. Here, we report two cases of subcalcaneal bursitis, and the first case of heel fat pad and subcalcaneal bursa herniation in patients with established RA, along with a comprehensive literature review of subcalcaneal bursitis and other heel fat pad abnormalities in RA. Subcalcaneal bursitis, also referred to as panniculitis, inflammatory-edematous lesion, or adventitial (adventitious) bursitis has been reported in up to 10% of patients with RA. It appears as a compressible, heterogeneous, and hypoechoic subcalcaneal mass on ultrasound (US), with peripheral vascularization on Doppler US. Patients may present with heel discomfort. Ultrasonographic assessment is usually sufficient to confirm the presence of heel fat pad pathologies. Rest, analgesics, and mechanical aids with or without addition of disease-modifying antirheumatic drugs are usually employed, while intervention is rarely required.

A previously healthy octogenarian presented with new onset heart failure symptoms. Comprehensive multimodality imaging including complete echocardiography with longitudinal strain analysis, cardiac magnetic resonance imaging (cMRI), nuclear medicine pyrophosphate (99-mcTcPYP) scan along with biomarker, monoclonal protein analysis, and fat pad biopsy confirmed diagnosis of transthyretin cardiac amyloidosis.

Background Atrial fibrillation (AF) is the most common arrhythmia occurring in humans, and new treatment strategies are critically needed. The lack of reliable preclinical animal models of AF is a major limitation to drug development of novel antiarrhythmic compounds. Objective The purpose of this study was to provide a comprehensive head-to-head assessment of 5 canine AF models. Methods Five canine models were evaluated for the efficacy of AF induction and AF duration. We tested 2 acute models: short-term atrial tachypacing (AT) for 6 hours with analysis of AF at hourly increments, and carbachol injection into a cardiac fat pad followed by short-term AT. We also tested 3 chronic models: pacemaker implantation followed by either 4 weeks of AT and subsequent atrial burst pacing or intermittent long-term AT for up to 4–5 months to generate AF ≥4.5 hours, and finally ventricular tachypacing to induce heart failure followed by atrial burst pacing to induce AF. Results Careful evaluation showed that acute AT, AT for 4 weeks, and the heart failure model all were unsuccessful in generating reproducible AF episodes of sufficient duration to study antiarrhythmic drugs. In contrast, intermittent long-term AT generated AF lasting ≥4.5 hours in ∼30% of animals. The acute model using carbachol and short-term AT resulted in AF induction of ≥15 minutes in ≥75% of animals, thus enabling testing of antiarrhythmic drugs. Conclusion Intermittent long-term AT and the combination of local carbachol injection with successive short-term AT may contribute to future drug development efforts for AF treatment.

International audience; Obesity is a complex disease with many causes, including a possible role for environmental chemicals. Perfluorohexane sulfonate (PFHxS) is one of many per- and polyfluoroalkyl substances (PFASs) frequently detected in humans and it is suspected to be an obesogenic compound. We examined the potential long-term effects of PFHxS on metabolic parameters in rats after developmental exposure to 0.05, 5 or 25 mg/kg bw/day, with or without co-exposure to a background mixture of twelve endocrine disrupting chemicals (EDmix). Both male and female offspring showed signs of lower birth weight following intrauterine exposure. Female offspring exposed to both PFHxS and EDmix had increased body weight in adulthood. The retroperitoneal fat pad was larger in the PFHxS-exposed female offspring when compared to those exposed to EDmix alone. An attempt to detect putative molecular markers in the fat tissue by performing whole transcriptome profiling revealed no significant changes between groups and there were no significant effects on plasma leptin levels in exposed females. Our results show that early life exposure to endocrine disrupting chemicals can influence body weight later in life, but the effect is not necessarily reflected in changed gene expression in the fat tissue.

This present research investigated the anti-obesity and hepatoprotective effects of ethanolic Moringa peregrina leaf (MPLE) and bark extracts (MPBE), in the rats fed with a high-fat diet (HFD). Healthy male rats (n = 48) were randomly distributed to six groups (n = 8): control AIN-93 diet; HFD; HFD + MPBE bark extracts ((300 mg/kg); HFD + MPBE (600 mg/kg); HFD + MPLE (300 mg/kg); HFD + MPLE (600 mg/kg). HFD-fed rats in the Moringa peregrina (MP) treatment groups received orally administered MP leaf or bark extract daily for eight weeks. The results revealed that both doses of MP leaf extract significantly reduced HFD-induced increases in their food intake and the gained body weight, fat pad weights (visceral, subcutaneous, and epididymal), glucose and insulin plasma levels, and leptin and resistin serum levels in HFD-fed rats. Concomitantly, MP leaf extract improved glucose levels after oral or intraperitoneal glucose tolerance tests, reduced serum cholesterol, triglycerides, and the low-density lipoprotein LDL concentration, reduced hepatic triglycerides and cholesterol levels, and increased serum high-density lipoproteins HDL levels and triglycerides and cholesterol levels in fecal. Moreover, the administration of MPLE to HFD-fed rats improved liver architecture, reduced fat accumulation, reduced hepatic malondialdehyde, tumor necrosis factor-α, and interleukin-6 levels. Hepatic glutathione peroxidase, superoxide dismutase, and catalase activities were significantly increased. All observed effects were more pronounced in HFD-fed rats treated with a 600 mg/kg MP dose. However, neither dose of MPBE altered the measured markers in the HFD-fed rats. In conclusion, MPLE showed potential anti-obesity and hepatoprotective activity in HFD-induced obese rats, mediated by reduced lipid absorption, anti-hyperlipidemic effects, and hepatic antioxidant effects.

Background and Objective: The prevalence of obesity is increasing both worldwide and locally in India. It is considered a major health problem and often leads to other associated diseases such as type 2 diabetes, ischemic heart diseases, stroke and cancer. In the present study, the effects of powder of Rosa damascena flowers on high-fat diet-induced obesity in Wistar albino rats were examined. Materials and Methods: Female Wistar albino rats fed with a High Fat Diet (HFD) (p.o) for 6 weeks were used to induce obesity. Powder of R. damascena (214 mg kg–1 b.wt.) petals administered orally to HFD-fed rats for 6 weeks. Physiological parameters like body weight, food and water intake, fat pad analysis and biochemical parameters like serum lipids, glucose, Serum Glutamate Oxaloacetate Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT), serum urea and creatinine levels were measured. Results: Treatment with powder of R. damascena flower petals to HFD-induced obese rats resulted in a significant reduction in body weight gain, fat pads, serum lipids, glucose, SGOT, SGPT and creatinine levels as compared to rats fed HFD alone. Further, the extract also showed a significant increase in High-Density Lipoprotein (HDL) levels. Conclusion: These results exhibit that the R. damascena flower possesses significant anti-obesity potential.

Localized adiposity is not only a common aesthetic issue but also a health risk factor. Pharmacopuncture can be a therapeutic option for the imbalance of regional fat distribution. The tuber of Pinellia ternata has been prescribed as antitussive and expectorant as a traditional Korean medicine. This study investigated the effects of pharmacopuncture with P. ternata water extract (PT) on localized adiposity. Male C57BL/6J mice were fed on a high-fat diet (HFD) for 6 weeks. 100 μL of 10 mg/mL of PT was injected into the left-side inguinal fat pad, while saline was injected into the right-side inguinal fat pad as self-control. Treatments were performed 3 times per week for 4 weeks. The inguinal fat weight was analyzed by dual-energy X-ray absorptiometry. PT pharmacopuncture significantly decreased the weight of the inguinal fat pad. The adipocyte size was reduced with increases of lipolytic enzymes and lipophagy-related factors by PT pharmacopuncture. There was marked inhibition of lipid accumulation content in 3T3-L1 adipocytes by PT treatment. The expressions of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG) 5, ATG7, and LC3 were markedly increased by PT treatments in vivo and in vitro. This study suggests that pharmacopuncture of Pinellia ternata has ameliorative effects on adiposity by lipid catabolic effects via activating both lipolysis and lipophagy in a localized region.

Summary Objective Increased foot‐ground contact loading engenders adaptive glabrous skin thickening and can decrease mechanoreceptor acuity and alter plantar cutaneous sensation. There has not been any research on whether overweight and obesity are similarly associated with normal plantar cutaneous sensation scores in children. This study investigated the associations between normal plantar cutaneous sensation scores and weight status (i.e., healthy weight, overweight, and obesity) in a sample of youth. Methods Plantar sensation was tested among 122 participants aged 8 to 16 years (10.3 ± 1.8 years; 140.0 ± 11.2 cm; 44.2 ± 16.0 kg) across the forefoot, midfoot, and rearfoot using Semmes‐Weinstein pressure aesthesiometry (0.07 g and 0.4 g monofilaments). Weight status was determined using the Centers for Disease Control and Prevention growth charts. Age‐ and sex‐adjusted models were used to explore the relationships between normal plantar sensation scores and weight status. Significant two‐tailed tests were set at p < .05. Results Only obesity was inversely associated with normal plantar sensation scores on the left (β = −.241; p = .009) and right (β = −.222; p = .018) forefeet, left (β = −.322; p = .001) and right (β = −.253; p = .007) midfeet, and left (β = −.286; p = .002) and right (β = −.228; p = .014) wholefeet (relative to healthy weight) when using the 0.07 g monofilament. There was no association between obesity and plantar sensation when using the 0.4 g monofilament. Conclusions Obesity is associated with diminished light touch plantar sensation. Considering previously reported higher mechanical loading and the fact that Merkel cells and the Aβfibers that innervate them are superficial to the hypodermis, adaptive glabrous skin thickening (rather than fat pad thickness) may underlie this association. Contrary to previous suggestions, overweight is not associated with decreased plantar cutaneous sensation.

To investigate the role of adipose tissue in reproductive function and mammary gland development and function, we have examined lipodystrophic (LD) mice. LD mice of both sexes are sterile, but fertility can be restored with leptin injections. Mammary glands from lipodystrophic mice were rudimentary and lacked terminal end buds. Leptin-injected LD mice were able to become pregnant, showed normal pregnancy-associated glandular proliferation despite a smaller glandular area, were able to produce a small amount of milk that had grossly normal content of milk proteins and neutral lipids, but could not sustain pups to weaning. In order to separate the individual requirements for 1) adipokines such as leptin, 2) estradiol, and 3) physical epithelial-adipocyte interactions, we performed a series of experiments with both lipodystrophic mice and ob (obese mice with a mutation in the lep gene encoding the adipokine leptin) mice that received either estradiol treatment or preadipocyte transplant. The resulting fat pad did not rescue the defect in mammary gland development in lipodystrophic mice. The defect also could not be rescued with estradiol pellets. Ob/ob mice, like LD mice, lack leptin and estradiol, but retain adipose tissue. Ob mice have defective mammary gland development. However, in striking contrast to what was observed in lipodystrophic mice, reconstitution of a WT fat pad in ob mice rescued the defect in mammary gland development. Estradiol treatment did not rescue mammary gland development in ob mice. Therefore direct interaction between mammary gland epithelia and adipocytes is a requirement for full invasion and expansion of the gland, but is not required for glandular proliferation during pregnancy and milk production.

Objective This study aimed to investigate the potential antiobesity effect of genetically modified Escherichia coli Nissle 1917 (EcN-GM) in mice fed a high-fat diet (HFD). Methods The mice were randomly divided into six groups: a normal diet group (ND), a HFD group, a HFD + EcN group, and three HFD + EcN-GM groups. The effects of EcN-GM on body weight, food intake, fat pad and organ weight, and an oral glucose tolerance test were measured, in addition to hepatic biochemistry and histological analysis. The mRNA expression of neuropeptides related to food intake regulation in the hypothalamus was also detected. Results The results showed that EcN-GM decreased body weight, body weight gain, food intake, fat pad weight, and hepatic weight of HFD mice. There were beneficial effects of EcN-GM on blood glucose, hepatic biochemistry, and hepatic histological alterations. A dramatic switch of food intake-regulating gene expression in the hypothalamus was also observed in mice. Conclusions This work has revealed that a modified live bacterial therapeutic, EcN-GM, has potential beneficial effects on obesity. This effect may be related to the regulating of the neuropeptide expression of energy intake and expenditure in the hypothalamus. This study demonstrates a successful example of engineered EcN-GM as a novel approach for weight management.

Fibrinogen-like-protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m2 ; n = 134) or without obesity (BMI

Disruption of biological rhythms due to exposure to artificial light at night (ALAN) has emerged as a new risk factor for metabolic diseases. However, the effects of ALAN exposure on energy metabolism with concomitant misalignment in the circadian system caused by nutritional imbalance remain largely unexplored. Here, we evaluate whether a low-protein (LP) diet could enhance the effects induced by exposure to ALAN on the energy metabolism and consequently predispose to metabolic disorders. Male C57BL6/J mice were weaned on a normal protein (NP) or a LP diet and housed on 12 h light:12 h darkness (LD) cycle. After 6 weeks, mice maintained on their respective diets were subdivided into normal light/darkness cycle (NP/LD; LP/LD) or exposed to ALAN (NP/LL; LP/LL) for 8 weeks. We observed that exposure to ALAN concomitant to LP diet disrupts the behavioral rhythms, without shifting the timing of food intake. Furthermore, exposure to ALAN leads to increased body and fat pad weights, higher levels of fast and fed glycemia and glucose intolerance independent of the diet consumed. Importantly, the effects of ALAN on circadian regulation of insulin sensitivity were diet-dependent with LP/LL mice showing insulin resistance in an opposite time of day than NP/LL. At the molecular level, exposure to ALAN concurrent with LP diet increased the expression of phosphoenolpyruvate carboxykinase 1 in both periods analyzed and inverted the pattern of fibroblast growth factor 21 (Fgf21) expression in the liver. Our data suggest that dietary protein restriction modulates the effects induced by nighttime light exposure on glucose metabolism, which could be partially related with the dysregulation of hepatic Fgf21 expression.

Localized adiposity is a serious aesthetic problem and a well-known health risk factor. There is a growing interest in minimally invasive treatment options for excessive fat accumulation, such as pharmacopuncture. LIPOSA is a newly developed pharmacopuncture formula from three natural herbs: The tuber of Pinellia ternata (Thunb.) Breitenb., the whole plant of Taraxacum platycarpum Dahlst. and the root of Astragalus membranaceus Bunge. The present study investigated the effects of pharmacopuncture treatment with LIPOSA on localized adiposity. Male C57BL/6J mice were fed high fat diet for 8 weeks to induce obesity. Then, 100 µl LIPOSA was injected into the left-side inguinal fat pad at various concentrations, including 13.35, 26.7 and 53.4 mg/ml. Normal saline was injected into the right-side inguinal fat pad of each mouse as a control. The treatment was performed three times per week for 2 weeks. The weight and histological changes were analyzed in the inguinal fat pad of the obese mice. The expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG)5, ATG7 and LC3-II, as lipophagy-related factors, were evaluated to confirm the lipid-catabolic effects of LIPOSA. LIPOSA pharmacopuncture markedly decreased the weight of the fat tissue and the size of the adipocytes in the inguinal region of the mouse models of obesity in a dose-dependent manner. The expression levels of ATGL, HSL, ATG5, ATG7 and LC3-II were significantly increased by the LIPOSA treatments. In addition, LIPOSA pharmacopuncture was found to decrease the expression levels of ACC, PPAR-γ and PEPCK. The results indicated that subcutaneous injection of LIPOSA can degrade local fat and induce lipophagic and lipase activation effects. In addition, lipid metabolism related to fat accumulation was regulated by the LIPOSA treatment. The present study suggests that LIPOSA pharmacopuncture can be a non-surgical alternative in the treatment of localized adiposity.

Pericardial fat pad in transverse sinus adjacent to left atrial appendage (LAA) is a rare condition that may resemble LAA thrombosis especially in suspected cases. More Trans‐esophageal echocardiography (TEE) angulations and also 3D TEE images are helpful tools to confirm the diagnosis.

Objective Intermittent fasting (IF) may limit metabolic adaptations that reduce energy expenditure, potentially by stimulating white adipose tissue (WAT) browning. The aim of this study was to examine the effects of 8 wk of IF on energy metabolism and markers of WAT browning in lean and diet-induced obese mice and in women who were overweight or obese. Methods Male C57 BL/6 J mice were fed chow or a high-fat diet (HFD; 43%) for 8 wk before undergoing IF (3 non-consecutive d/wk) for an additional 8 wk. Food intake, energy expenditure, and inguinal and gonadal fat pads were collected in fed or fasted conditions (22 h, IF mice only). Subcutaneous adipose tissue (SAT) was also collected at baseline, and after 8 wk of IF (in the fed state, and after a 24-h fast), in women with overweight or obesity. Uncoupling protein 1 (UCP1) was assessed by quantitative real-time polymerase chain reaction (mice and humans) and immunohistochemistry (mice). Results IF reduced body weight and energy intake in HFD fed mice and reduced gonadal and inguinal fat pad weights in both diet groups. IF increased energy expenditure, meal number, Ucp1 mRNA levels in inguinal and gonadal fat depots, and UCP1 protein in inguinal fat in both diet groups on fed days. In women, IF reduced body weight and fat mass, but did not alter UCP1mRNA levels. Conclusions IF increased energy expenditure and promoted WAT browning in mice but did not alter UCP1 mRNA levels in SAT in women.

Objective: To investigate the changes of Notch-1 protein expression and the changes of Notch-1 and NICD contents in the sinoatrial node fat pad (SAN-FP) nerve plexus of canines with chronic atrial fibrillation in which atrial fibrillation of the left atrium was induced in chronic pacing canines, in order to elucidate the relationship between the Notch signaling pathway of the SAN-FP nerve plexus and the occurrence and development of atrial fibrillation. Methods: Healthy Beagle dogs weighing 18 ± 2.66 kg, aged 7 to 9 years were randomly divided into a sham operation (SO) group (n = 5) and an atrial fibrillation (AF) group (n = 5), respectively. Results: Atrial fibrillation was successfully induced in canines in the AF group by rapid pacing on the left atrium appendage. The scattered nerve plexus was observed in fat cells of the SAN-FP. In contrast with the SO group, Notch-1 protein expression in the AF group was significantly increased (P < 0.05). No significantly statistical differences were observed in the concentration of Notch-1 and NICD between the AF group and the SO group (P > 0.05). In addition, no statistical differences in baseline Notch-1 and NICD concentrations were observed between the AF group and the SO group (P > 0.05). After an 8-week study, the concentrations of Notch-1 and NICD in the AF group were significantly increased compared with the SO group (P < 0.05). Conclusion: During the occurrence and development of AF, Notch-1 was expressed in different phases in the SAN-FP nerve plexus. After combining with ligands, Notch-1 was activated as NICD to affect the downstream target genes.

Tributyltin chloride (TBT) is an obesogen associated with several complications. However, few investigations have evaluated TBT effects on adult mammary glands (MG). In this investigation, we assessed whether TBT's obesogenic effects resulted in abnormal MG fat pad expansion and other irregularities. TBT was administered to female rats (100 ng/kg/day for 15 days via gavage), and their MG morphophysiological development was assessed. We further assessed the MG fat pad for PPARγ, ERα, and aromatase protein expression, as well as inflammation, oxidative stress (OS), apoptosis and fibrosis. Irregular MG morphological development such as lower TEB number, alveolar (AB), lobule and differentiation (DF) score were observed in TBT rats. TBT rats had abnormal MG fat accumulation as evidenced by increased numbers of hypertrophic adipocytes, triglyceride (TG) levels and PPARγ expression. A strong negative correlation between the MG obesogenic makers and TEB number, AB and DF score were observed in TBT rats. MG inflammation was observed in TBT rats. A positive correlation between the MG obesogenic markers and inflammation were observed. High ERα and aromatase expression were observed in MG of TBT rats. MG OS, apoptosis and fibrosis were present in the TBT rats. Additionally, a positive correlation between the MG obesogenic markers and OS were observed in TBT rats. Thus, these data suggest that obesogenic TBT effects led to MG irregularities in the adult female rats.

Microtubule-actin cross-linking factor-1 (ACF7, or MACF1) regulates cytoskeletal focal adhesion dynamics and migration in various tissues. High fat diet (HFD) induces gut microbiota dysbiosis and metabolic disorders, and increases intestinal permeability and inflammatory response. Here we investigated the synergistic effects of intestinal ACF7 conditional knockout (ACF7 cKO) and HFD on metabolism phenotypes, gut microbiota and intestinal barrier function in mice. ACF7 cKO and control (ACF7fl/fl) mice (8-week-old) were fed with either chow diet or HFD, for 16 weeks. The increase of body weight and fat pad weight were impaired in HFD-fed ACF7 cKO mice, which can be attributed to decreased food intake and absorption. The metabolic status of HFD-fed ACF7 cKO mice was dramatically changed when compared to the other groups. In addition, HFD-fed ACF7 cKO mice had increased epithelial cell apoptosis, intestinal permeability and inflammatory response when compared with the other groups. The ACF7 cKO-induced changes in alimentation, intestinal barrier function, and gut microbiota were independent of dietary treatment. Taken together, our studies for the first time proved HFD and ACF7 cKO have synergistic damaging effects on intestinal homeostasis. ACF7 is a crucial protective molecule in HFD-induced intestinal diseases.

The present study was conducted to investigate the effect of feeding the different levels of the dietary fat on the expression of genes encoding proteins involving energy metabolism, oxidative phosphorylation, and lipid synthesis including peroxisome proliferator-activated receptor gamma (PPARγ) of laying hens in the intestine. Birds fed diets with 3 levels of fat, that is, low (LF), medium (MF), and high fat (HF) were reared from 22 to 42 wk of age. Jejunum tissue was collected at week 42 for gene expression analysis. Dietary fat content as ether extract, net energy to AME ratio, and CP content of 3 treatment groups were as follows: LF: 25, 0.735, 187 (g/kg, DM); MF: 61, 0.739, 185 (g/kg, DM); HF: 73, 0.752, 181 (g/kg, DM). The BW, fat pad weight (g), fat pad–to–BW ratio (%) was the same for all the treatments (P > 0·05). Birds fed a diet containing HF increased the AME daily intake per metabolic BW (BW0.75) (P 0·05). The mitochondrial count per cell showed no difference among the 3 groups with different dietary treatments (P > 0·05). The results suggest that PPARγ may be important to the energy expenditure during nutrient absorption, digestion, and metabolism, and respiratory chain complexes, and other genes involving mitochondrial energy metabolism and lipogenesis may be less responsive to dietary treatment.

Background: Diabetic foot disease is associated with physiological and biomechanical abnormalities in the foot that increase risk for ulceration. The objective was to assess MRI changes in the composition of sub-calcaneal fat pad tissue and its association with plantar pressure during walking. Methods: Fourteen people with diabetes and peripheral neuropathy and five age-matched healthy controls underwent T1-weighted sagittal plane spin-echo Dixon MRI of the rearfoot. Dixon Chemical Shift Imaging was used to create fat-only and water-only images from which the fat signal fraction in a defined ROI of the sub-calcaneal fat pad was calculated. Barefoot plantar pressure distribution during walking was assessed and associated with fat pad outcomes. Findings: Mean ± SD fat signal fraction was significantly lower in the neuropathic subjects than in the healthy controls (0.55 ± 0.11 vs. 0.72 ± 0.03, p < 0.005), and was explained by a lowering in fat signal (R 2 0.87), more than an increase in water signal (R 2 0.32). Mean ± SD peak pressure at the heel was 391 ± 119 kPa for the neuropathic subjects and 325 ± 53 kPa for the healthy controls (non-significantly different). Fat signal fraction and peak pressure were significantly inversely correlated (r = −0.59, p < 0.01). Interpretation: Dixon chemical shift MRI showed a reduced fat signal fraction in sub-calcaneal fat pad tissue in people with diabetic neuropathy. Both neuropathic and non-neuropathic factors may be attributed to this outcome. Fat pad function also seems to be compromised, as indicated by an associated increase in peak plantar pressures. This may increase risk for foot ulceration.

Metabolic syndrome prevalence has increased among US adults, particularly among non-hispanic white and black women. Sedentary behavior often leads to chronic inflammation, a triggering factor of metabolic syndrome. Given that intrinsic exercise capacity is genetically inherited, we questioned if low-grade chronic inflammation would be present in a female rat model of low intrinsic exercise capacity-induced metabolic syndrome, while beneficial increase of resolution of inflammation would be present in a female rat model of high intrinsic exercise capacity. In the vascular system, two primary markers for inflammation and resolution of inflammation are cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Our study focused on the novel hypothesis that untrained, inherited exercise capacity induces divergent vascular plasticity via changes in the delicate balance between COX and LOX inflammatory mediators. We used divergent rat strains with low (LCR) and high (HCR) aerobic running capacity. By using animals with contrasting intrinsic exercise capacities, it is possible to determine the exact triggers that lead to inherited vascular plasticity in female rats. We observed that female LCR displayed increased periovarian fat pad and body weight, which is congruent with their obesity-presenting phenotype. Furthermore, LCR presented with vascular hypocontractility and increased COX and LOX-derived pro-inflammatory factors. On the other hand, HCR presented with a "shutdown" of COX-induced vasoconstriction and enhanced resolution of inflammation to maintain vascular tone and homeostasis. In conclusion, LCR display low-grade chronic inflammation via increased COX activity. These results provide mechanistic clues as to why lower intrinsic aerobic capacity correlates with a predisposition to risk of vascular disease. Conversely, being born with higher intrinsic aerobic capacity is a significant factor for improved vascular physiology in female rats.

Glucosyl hesperidin (GH) is a water-soluble derivative of hesperidin, a citrus flavonoid. GH has various pharmacological effects, such as hypolipidemic and hypouricemic effects, and may therefore be a useful supplement or drug. In the present study, we evaluated the effects of long- and short-term intake of GH on hyperglycemia and macrophage infiltration into the adipose tissue of high-fat diet (HFD)-fed mice. Long-term (11-week) consumption of GH tended to reduce body weight and the fasting blood glucose concentration of the HFD-fed mice, and ameliorated glucose intolerance and insulin resistance, according to glucose and insulin tolerance tests. Additionally, although GH did not affect fat pad weight, it reduced HFD-induced macrophage infiltration into adipose tissue. Short-term (2-week) consumption of GH did not affect the HFD-induced increases in body weight or fasting blood glucose, and it did not ameliorate glucose intolerance or insulin resistance. However, short-term intake did reduce the HFD-induced macrophage infiltration and monocyte chemotactic protein 1 (MCP-1) expression in adipose tissue. Furthermore, hesperetin, which is an aglycone of GH, inhibited MCP-1 expression in 3T3-L1 adipocytes, 3T3-L1 adipocytes co-cultured with RAW264 macrophages, and tumor necrosis factor-α-treated 3T3-L1 adipocytes. The present findings suggest that daily consumption of GH may have preventive and/or therapeutic effects on obesity-related diseases, such as diabetes mellitus.

Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of ADSCs-derived adipocytes. The rats were divided into four groups: normal diet (ND)-fed control (ND-SED), ND-fed TR (ND-TR), HFD-fed control (HFD-SED), and HFD-fed TR (HFD-TR). After 9 weeks of intervention, ADSCs of epididymal and inguinal adipose tissues were differentiated into adipocytes. In the metabolome analysis of adipocytes after isoproterenol stimulation, 116 metabolites were detected. The principal component analysis demonstrated that ADSCs-derived adipocytes segregated into four clusters in each fat pad. Amino acid accumulation was greater in epididymal ADSCs-derived adipocytes of ND-TR and HFD-TR, but lower in inguinal ADSCs-derived adipocytes of ND-TR, than in the respective controls. HFD accumulated several metabolites including amino acids in inguinal ADSCs-derived adipocytes and more other metabolites in epididymal ones. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that TR mainly affected the pathways related to amino acid metabolism, except in inguinal ADSCs-derived adipocytes of HFD-TR rats. These findings provide a new way to understand the mechanisms underlying possible changes in the differentiation of ADSCs due to TR or HFD.

Injection lipolysis or mesotherapy gained popularity for local fat dissolve as an alternative to surgical liposuction. Phosphatidylcholine (PPC) and aminophylline (AMPL) are commonly used compounds for mesotherapy, but their efficacy and safety as lipolytic agents have been controversial. Glycerophosphocholine (GPC) is a choline precursor structurally similar to PPC, and thus introduced in aesthetics as an alternative for PPC. This study aimed to evaluate the effects of GPC on adipocytes differentiation and lipolysis and compared those effects with PPC and AMPL using in vitro and in vivo models. Adipogenesis in 3T3-L1 was measured by Oil Red O staining. Lipolysis was assessed by measuring the amount of glycerol released in the culture media. To evaluate the lipolytic activity of GPC on a physiological condition, GPC was subcutaneously injected to one side of inguinal fat pads for 3 days. Lipolytic activity of GPC was assessed by hematoxylin and eosin staining in adipose tissue. GPC significantly suppressed adipocyte differentiation of 3T3-L1 in a concentration-dependent manner (22.3% inhibition at 4 mM of GPC compared to control). Moreover, when lipolysis was assessed by glycerol release in 3T3-L1 adipocytes, 6 mM of GPC stimulated glycerol release by two-fold over control. Subcutaneous injection of GPC into the inguinal fat pad of mice significantly reduced the mass of fat pad and the size of adipocytes of injected site, and these effects of GPC were more prominent over PPC and AMPL. Taken together, these results suggest that GPC is the potential therapeutic agent as a local fat reducer.

BackgroundObesity, reached epidemic proportions globally is often associated with life threatening comorbidities. The unavailability of safe and effective long term medications for obesity in modern pharmacotherapy forces the scientific community to explore the potential of Ayurvedic traditional healers as they are considered safe and effective.ObjectiveTo explore the anti-obesity potential of aqueous extract of aerial parts ofAchyranthes asperaL. (AEAA), a traditional healer in high fat diet (HFD) induced obese rats.MethodsAEAA was prepared and subjected to in-vitro pancreatic lipase inhibition assay and in-vivo anti-obesity studies. For in-vivo studies, HFD fed obese prone Wistar albino rats were divided into five experimental groups (Group II to VI): animals fed with standard pellet chow served as normal control (Group I) while, animals continued with HFD alone served as obese control (Group II); Group III, IV and V were administered AEAA at a dose of 100, 200 and 300 mg/kg b.w. respectively along with HFD; and animals administered orlistat (30 mg/kg bw) along with HFD served as standard control (Group VI). All the drugs were administered orally once a day for a period of 60 days. At the end of the experimental period various physical, biochemical and histopathological observations were made.ResultsIn-vitro studies showed AEAA partially but not significantly inhibited the activity of pancreatic lipase. Data of in-vivo studies revealed, significant reduction in body weights, fat pad weights and organ weights upon AEAA treatment. Elevated levels of glucose, insulin, leptin, lipid profiles and antioxidant status were also brought back to normal.ConclusionThe obtained results clearly suggested that AEAA possess pronounced anti-obesity potential.

Background The diagnostic accuracy of histopathological detection of transthyretin amyloid (ATTR) by Congo red staining of abdominal fat samples has been questioned since low sensitivity has been reported, especially for patients with ATTR cardiomyopathy. However, the outcome of surgically obtained fat pad biopsies has not yet been evaluated. The aim was to evaluate the diagnostic accuracy of skin punch biopsies from abdominal fat in patients with suspected ATTR amyloidosis. Material and methods Data were evaluated from patients who had undergone abdominal fat pad biopsies using a skin punch due to suspected amyloidosis from 2006 to 2015. The biopsies had been analysed using Congo red staining to determine the presence of amyloid, and immunohistochemistry or Western blot to determine the type of amyloidosis. The final diagnosis was based on the clinical picture, biopsy results and DNA sequencing. Minimum follow-up after the initial biopsy was 3 years. Results Two hundred seventy-four patients (61% males) were identified, and in 132 (48%), a final diagnosis of amyloidosis had been settled. The majority (93%) had been diagnosed with hereditary transthyretin (ATTRv) amyloidosis, and therefore subsequent analyses were focused on these patients. Overall, our data showed a test specificity of 99% and a sensitivity of 91%. Ninety-eight (94%) of the patients had neuropathic symptoms at diagnosis, whereas 57 (55%) had signs of amyloid cardiomyopathy. Subgroup analyses showed that patients with merely neuropathic symptoms displayed the highest test sensitivity of 91%, whereas patients with pure cardiomyopathy displayed the lowest sensitivity of 83%. However, no significant differences in sensitivity were found between patients with or without cardiomyopathy or between the sexes. Conclusions Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspect ATTRv amyloidosis, including patients presenting with cardiomyopathy. In addition, the method enables typing not only of the precursor protein but also of the amyloid fibril type, which is related to the phenotype and to the outcome of the disease.

Brown adipose tissue (BAT) is an important target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH) converts bioactive epoxy fatty acids (EpFAs) into less active diols. sEH inhibitors (sEHI) are beneficial in many chronic diseases by stabilizing EpFAs. However, roles of sEH and sEHI in brown adipogenesis and BAT activity in treating diet-induced obesity (DIO) have not been reported. sEH expression was studied in in vitro models of brown adipogenesis and the fat tissues of DIO mice. The effects of the sEHI, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy-benzoic acid (t-TUCB), were studied in vitro and in the obese mice via mini osmotic pump delivery. sEH expression was increased in brown adipogenesis and the BAT of the DIO mice. t-TUCB promoted brown adipogenesis in vitro. Although t-TCUB did not change body weight, fat pad weight, or glucose and insulin tolerance in the obese mice, it decreased serum triglycerides and increased protein expression of genes important for lipid metabolism in the BAT. Our results suggest that sEH may play a critical role in brown adipogenesis, and sEHI may be beneficial in improving BAT protein expression involved in lipid metabolism. Further studies using the sEHI combined with EpFA generating diets for obesity treatment and prevention are warranted.

Lipid overload of the adipose tissue, which can be caused by overnutrition, underlies metabolic disease. We hypothesized that increasing the energy demand of adipose tissue is a promising strategy to combat excessive lipid accumulation. Resveratrol, a natural polyphenol, activates lipid catabolism in fat tissue; however, its clinical success is hindered by poor bioavailability. Here, we implanted resveratrol releasing poly(lactide-co-glycolide) scaffolds into epididymal fat to overcome its poor bioavailability with the goal of enhancing local lipid catabolism. In lean mice, resveratrol scaffolds decreased adipocyte size relative to scaffolds with no drug, a response that correlated with AMP kinase activation. Immunohistochemistry indicated that macrophages and multinucleated giant cells within the scaffold expressed carnitine palmitoyltransferase 1 (CPT1) at higher levels than other cells in the adipose tissue. Furthermore, resveratrol increased CPT1 levels in cultured macrophages. Taken together, we propose that resveratrol scaffolds decrease adipocyte size because resveratrol increases lipid utilization in scaffold-infiltrating immune cells, possibly through elevating CPT1 levels or activity. In a follow-up study, mice that received resveratrol scaffolds 28-days prior to a high fat diet exhibited decreased weight gain, adipose tissue expansion, and adipocyte hypertrophy compared to mice with control scaffolds. Notably, this scaffold-based strategy required a single resveratrol administration compared to the daily regiment generally needed for oral administration. These results indicate that localized delivery of metabolism modulating agents to the adipose tissue may overcome issues with bioavailability and that the role of biomaterials should be further investigated in this therapeutic strategy for metabolic disease.

Background The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P P P P P P P P Conclusion These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.

The present study was designed to investigate the effect of embelin in metabolic endotoxemia (ME) mediated inflammation and associated obesity in high fat diet (HFD)-fed C57BL/6 mice. The molecular docking of embelin confirms its binding with the toll-like receptor-4 (TLR-4). In vivo study, mice were treated with HFD for 8 weeks to induce ME mediated inflammation and associated obesity. Further, mice were treated with embelin (50 and 100 mg/kg/day, p.o.) and orlistat (10 mg/kg/day, p.o.) from 5th to 8th week along with HFD to improve associated changes. After 8 weeks, mice were euthanized and assessed for body weight, body mass index (BMI), fat pad weights (mesenteric, retroperitoneal, and epididymal), intestinal permeability, TLR-4, tumor necrosis factor-α, interleukin-6, lipopolysaccharide, and serum lipid levels followed by histopathological analysis of liver and adipose tissues. Embelin significantly decreased the body weight, BMI, serum lipid levels, ME, and inflammation manifested by above parameters. Further, results of histopathological study showed that embelin restored the vacuolization, inflammation, one side shifting of nucleus in liver tissue, and decreased adipocyte cells size in adipose tissue in HFD-fed mice. Thus, our findings provide the strong evidence first time that embelin could modulate ME, mediate inflammation, and consequently reduce body weight gain, BMI, and serum lipid levels in HFD-fed mice.

Background The insulin-sensitizing phytocannabinoid, Δ(9)-tetrahydrocannabivarin (THCV) can signal partly via G-protein coupled receptor-55 (GPR55 behaving as either an agonist or an antagonist depending on the assay). The cannabinoid receptor type 1 (CB1R) inverse agonist rimonabant is also a GPR55 agonist under some conditions. Previous studies have shown varied effects of deletion of GPR55 on energy balance and glucose homeostasis in mice. The contribution of signalling via GPR55 to the metabolic effects of THCV and rimonabant has been little studied. Methods In a preliminary experiment, energy balance and glucose homeostasis were studied in GPR55 knockout and wild-type mice fed on both standard chow (to 20 weeks of age) and high fat diets (from 6 to 15 weeks of age). In the main experiment, all mice were fed on the high fat diet (from 6 to 14 weeks of age). In addition to replicating the preliminary experiment, the effects of once daily administration of THCV (15 mg kg−1 po) and rimonabant (10 mg kg−1 po) were compared in the two genotypes. Results There was no effect of genotype on absolute body weight or weight gain, body composition measured by either dual-energy X-ray absorptiometry or Nuclear Magnetic Resonance (NMR), fat pad weights, food intake, energy expenditure, locomotor activity, glucose tolerance or insulin tolerance in mice fed on chow. When the mice were fed a high fat diet, there was again no effect of genotype on these various aspects of energy balance. However, in both experiments, glucose tolerance was worse in the knockout than the wild-type mice. Genotype did not affect insulin tolerance in either experiment. Weight loss in rimonabant- and THCV-treated mice was lower in knockout than in wild-type mice, but surprisingly there was no detectable effect of genotype on the effects of the drugs on any aspect of glucose homeostasis after taking into account the effect of genotype in vehicle-treated mice. Conclusions Our two experiments differ from those reported by others in finding impaired glucose tolerance in GPR55 knockout mice in the absence of any effect on body weight, body composition, locomotor activity or energy expenditure. Nor could we detect any effect of genotype on insulin tolerance, so the possibility that GPR55 regulates glucose-stimulated insulin secretion merits further investigation. By contrast with the genotype effect in untreated mice, we found that THCV and rimonabant reduced weight gain, and this effect was in part mediated by GPR55.

The fat pad defined as the epididymal fat is located at the head part of the epididymis. However, another fat mass is present near the caudal epididymis, named tail epididymal fat. The present research was focused to determine the expression of adipocyte-associated molecules in the mouse tail epididymal fat at different postnatal ages, including 2, 5, 8, and 12 months of age. The quantitative real-time PCR analysis showed continuous increases of expression levels of delta like non-canonical Notch ligand 1, leptin, and resistin as postnatally aged. The transcript level of peroxisome proliferator-activated receptor gamma was the highest at 5 months of age, remaining at a steady level until 12 months of age. Expression levels of fatty acid binding protein 4, leptin, and adiponectin were significantly increased until 8 months of age, persisting the level at 12 months of age. The transcript level of fatty acid synthase was significantly increased at 8 months of age, without a further change of the level at 12 months of age. These findings exhibited the expression of adipocyte-associated genes which were also detected at the ordinary epididymal fat pad. However, expression patterns of these genes in the tail epididymal fat are different with those in the distal and proximal epididymal fat, suggesting distinct characteristics and/or functions of the tail epididymal fat.

Obesity is influenced by genetics and diet and has wide ranging comorbidities, including anxiety and depressive disorders. Outbred heterogeneous stock (HS) rats are used for fine-genetic mapping of complex traits and may be useful for understanding gene by diet interactions. In this study, HS rats were fed diets containing 60% kcal from fat (high-fat diet, HFD) or 10% kcal from fat (low-fat diet, LFD) and tested for metabolic ( study 1) and behavioral ( study 2) outcomes. In study 1, we measured glucose tolerance, fasting glucose and insulin, fat pad weights and despair-like behavior in the forced swim test (FST). In study 2, we assessed anxiety-like (elevated plus maze, EPM; open field test, OFT) and despair-like/coping (splash test, SpT; and FST) behaviors. Body weight and food intake were measured weekly in both studies. We found negative effects of HFD on metabolic outcomes, including increased body weight and fat pad weights, decreased glucose tolerance, and increased fasting insulin. We also found negative effects of HFD on despair-like/coping and anxiety-like behaviors. These include increased immobility in the FST, decreased open arm time in the EPM, and increased movement and rest episodes and decreased rearing in the OFT. The diet-induced changes in EPM and OFT were independent of overall locomotion. Additionally, diet-induced changes in OFT behaviors were independent of adiposity, while adiposity was a confounding factor for EPM and FST behavior. This work establishes the HS as a model to study gene by diet interactions affecting metabolic and behavioral health.

Background: Thyroid hormones have many effects on the physiological functions of cells, including growth, differentiation, and metabolism. Objectives: Recently, studies have shown that the adipose-derived mesenchymal stem cells conditioned medium (ADMSCs-CM) has many osteogenic factors, such as IGF-1, IL-6, and FGFs. Methods: In the current study, mesenchymal stem cells (MSCs) were isolated from two sources; the adipose tissue of the testicular fat pad and the bone marrow of rat, and then characterized by flow cytometry. ADMSCs-CM was collected from the ADMSC in the healthy adult male rats. Hypothyroidism was induced by the administration of the Methimazole during 60 days and confirmed by the analysis of the serum level of T4 and TSH hormones. Cell proliferation and osteogenic differentiation potential of bone marrow stem cells (BMSCs) derived from hypothyroid rats were investigated in the presence and absence of the CM by MTT assay, alkaline phosphatase (ALP) activity, calcium content assay, and bone-related gene expression. Healthy BMSCs were assigned to the control group. Results: Although Cell proliferation was decreased in the hypothyroid BMSCs, there was no significant difference between the control and the hypothyroid-CM groups. Similarly, osteogenic potential was significantly reduced in the hypothyroid group compared to the control and hypothyroid-CM groups according to the ALP, calcium content assays, and gene expression results. There was no significant difference between the hypothyroid-CM group and control. Conclusions: Our results indicated that hypothyroidism can decrease cell proliferation and osteogenic differentiation of BMSCs. Although ADMSCs-CM improved these parameters, it may be a promising candidate for the bone regeneration of the hypothyroidism cases.

Background: Transverse sinus (TS) is located anterior to the left atrium (LA) and almost posterior to the aortic root. Pericardial fat pad in transverse sinus adjacent to LAA is a rare condition that may resemble LAA thrombosis especially in suspected cases. Case presentation: A 60 years old woman with history of dyspnea on exertion and severe mitral stenosis was planned for percutaneous transvenous mitral commissurotomy (PTMC). In TEE imaging mass-like lesion near LAA was seen and was first thought to be LAA thrombosis. After more TEE angulations and 3D TEE the diagnosis of transverse sinus fat pad (TSFP) was confirmed. Conclusion: Along-side 2D imaging, 3D TEE we can better delineate the complex structure of LA and LAA.

Ectopic lipid accumulation, the deposition of lipids in lean tissue, is linked to type 2 diabetes through an association with insulin resistance. It occurs when adipose tissue fails to meet lipid storage needs and there is lipid spillover into tissues not equipped to store them. Ectopic lipid contributes to organ dysfunction because lipids can interfere with insulin signaling and other signaling pathways. Clinical studies indicate that decreasing ectopic lipids through diet and exercise is effective in treating type 2 diabetes; however, its prevalence continues to rise. We propose that strategies to improve lipid handling in the adipose tissue would be adjunctive to healthy lifestyle modification and may address difficulties in treating type 2 diabetes and other syndromes spurred by ectopic lipid. Herein, we investigate biomaterial implants as a means to increase lipid utilization in adipose tissue through the recruitment of highly metabolic cells. Poly(lactide-co-glycolide) scaffolds were implanted into the epididymal fat of mice fed a high fat diet that overwhelms the adipose tissue and promotes ectopic lipid accumulation. Over 5 weeks, mice with scaffolds gained less weight compared to mice without scaffolds and were protected from hyperinsulinemia. These effects correlated with a 53% decrease in triglyceride in the gastrocnemius and a 25% decrease in the liver. Scaffolds increased CPT1A protein levels in the epididymal fat and histology revealed high expression of CTP1A in the cells infiltrating the scaffold relative to the rest of the fat pad. In addition, lacing the scaffold with resveratrol increased CPT1A expression in the epididymal fat over scaffolds with no drug; however, this did not result in further decreases in weight gain or ectopic lipid. Mechanistically, we propose that the cellular activity caused by scaffold implant mitigates the lipid load imposed by the high fat diet and leads to a substantial decrease in lipid accumulation in the muscle and liver. In conclusion, this study establishes that a tissue engineering approach to modulate lipid utilization in the epididymal fat tissue can mitigate ectopic lipid accumulation in mice fed a high fat diet with positive effects on weight gain and whole-body insulin resistance.

ObjectiveTo evaluate the upper airway morphology changes associated with ageing in adult Chinese patients with obstructive sleep apnoea.MethodsA total of 124 male patients diagnosed with obstructive sleep apnoea by overnight polysomnography, who underwent upper airway computed tomography, were enrolled. The linear dimensions, cross-sectional area and volume of the upper airway region and the surrounding bony frame were measured. The association between ageing and upper airway morphology was analysed.ResultsSoft palate length, minimum cross-sectional area of the retroglossal region, lateral dimensions at the minimum cross-sectional area of the retropalatal and retroglossal regions, nasopharyngeal volume, and average cross-sectional area of the nasopharyngeal region were found to significantly increase with ageing in all patients, while the upper airway shape flattened with ageing. The volume of the retropalatal region increased with ageing among the patients with a body mass index of less than 24 kg/m2. The volume of parapharyngeal fat pad increased with ageing among patients with a body mass index greater than 28 kg/m2.ConclusionA number of dimensional, cross-sectional and volumetric parameters of the pharynx increased with age, indicating that non-anatomical factors may play a more important role in the pathogenesis of obstructive sleep apnoea in aged patients.

Zhitao Ren,1 Qingping Lan,1 Yan Chen,1 Yuet Wa Judy Chan,1 Gail B Mahady,2 Simon Ming-Yuen Lee1 1State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 2Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Center for Traditional Medicine, University of Illinois at Chicago, Chicago, IL, USACorrespondence: Simon Ming-Yuen LeeInstitute of Chinese Medical Sciences, University of Macau, Avenide Da Universidade, Room 7003, N22 Building, Taipa, Macau, People’s Republic of ChinaTel +853-88224695Email simonlee@umac.moObjective: Toevaluate the effect LMHFV on body weight gain, NAFLD and muscle strength and explore effect in mitochondrial biogenesis, AMPKα and p38 pathways.Methods: Vibration platform used in this study provides specific whole-body cyclic mechanical stimulation at low magnitude (0.3 g) and high frequency (50 Hz). Diabetic mice (8– 9 mice per group) (C57BL/KsJ-m+/+Leprdb) were randomly divided into untreated group (no vibration) and two vibration groups. Lean mice (8 mice) were used as non-diabetic control for both groups. Two diabetic vibration groups received LMHFV every day for 20 min/day and 40 min/day separately.Results: After 8weeks of treatment, results showed that body weight, liver weight, fat pad weight, glucose level and insulin level were lower in vibration group when compared with the untreated group. The ratio of fat in liver was significantly decreased after vibration treatment. Muscle strength was significantly increased after vibration. Mitochondrial biogenesis-related gene expression was increased in soleus, gastrocnemius and liver. AMPKα mRNA expression level was increased in soleus and gastrocnemius after vibration treatment. p38 and AMPKα mRNA expression level and protein expression level in liver were enhanced with vibration treatment. Moreover, phosphorylation of p38 and AMPKα was enhanced in liver.Conclusion: LMHFV applied in our study decreases body weight gain and improves muscle strength and NAFLD in diabetic mice which were partly through improving mitochondrial biogenesis by enhancing p38 and AMPKα pathway.Keywords: type 2 diabetes mellitus, low-magnitude high-frequency vibration, mitochondrial biogenesis, AMPKα, p38

Background The longer upper airway is more collapsible during sleep. This study aims to reveal relationships among upper airway length, weight, and obstructive sleep apnea (OSA), particularly to answer why the upper airway of OSA patients is longer than that of healthy people and why some obese people suffer from OSA while others do not. Methods We perform head and neck MRI on male patients and controls, and measure > 20 morphological parameters, including several never before investigated, to quantify the effect of weight change on upper airway length. Results The upper airway length is longer in patients and correlates strongly to body weight. Weight increase leads to significant fat infiltration in the tongue, causing the hyoid to move downward and lengthen the airway in patients. The apnea-hypopnea index (AHI) strongly correlates to airway length and tongue size. Surprisingly, a distance parameter h and angle β near the occipital bone both show significant differences between healthy males and patients due to their different head backward tilt angle, and strongly correlates with AHI. The contributions of downward hyoid movement and head tilt on airway lengthening are 67.4–80.5% and19.5–32.6%, respectively, in patients. The parapharyngeal fat pad also correlates strongly with AHI. Conclusions The findings in this study reveal that the amount of body weight and distribution of deposited fat both affect airway length, and therefore OSA. Fat distribution plays a larger impact than the amount of weight, and is a better predictor of who among obese people are more prone to OSA.

The non-therapeutic use of the androgenic anabolic steroid Nandrolone Decanoate is popular due to its effects on physical performance and body composition, especially for its lipolytic and anabolic effects associated. However, high doses of such drugs are often associated with a series of pathologies related to unbalanced redox homeostasis, which, in turn, can be linked to inflammation. The oxidative stress onset could deregulate the secretion of cytokines, evidencing a dysfunctional adipocyte. Thus, the aim of this study was to investigate the effect of supraphysiological doses of Nandrolone Decanoate on redox homeostasis of retroperitoneal fatpad of male rats and its relationship with cytokines-based inflammatory signaling. Hydrogen peroxide production was assessed in the retroperitoneal fat pad of adult male rats which received either 10 mg kg of Nandrolone Decanoate or only a vehicle. Also, catalase, superoxide dismutase and glutathione peroxidase activities were measured, together with total reduced thiols and protein carbonylation, as well as IL-1β, TNF-α, and IL-6 local levels. High doses of Nandrolone Decanoate caused an increase in the hydrogen peroxide production, together with lower activities of the antioxidant enzymes and lower levels of total reduced thiol. There were also higher protein carbonylation and greater levels of IL-1β, TNF-α, and IL-6 in the treated group compared to control group. Therefore, it was possible to verify that high doses of Nandrolone Decanoate cause oxidative stress and induce higher inflammatory signaling in retroperitoneal fat pad of male rats.

Introduction Our study goal was verification of shear-wave elastography (SWE) as an assessment tool enabling quantitative analysis of facial fat tissue elasticity, using the example of the deep medial cheek fat compartment (DMCFC), due to its major role in pseudoptosis etiology. Aim Furthermore, we determined the age-specific reference values for DMCFC elasticity and analyzed its correlation with body mass index (BMI) and DMCFC thickness. Material and methods The study included 89 female patients (age: 18-63 years, mean: 45.9 ±14.2 years) with intact facial skin. Prior to the procedure, all participants were subjected to SWE of the DMCFC. Reference ranges for elastographic parameters were defined as ± 2 standard deviations (SD), or estimated by means of ROC analysis. Results The DMCFC elasticity correlated inversely with DMCFC thickness (R = -0.292, p < 0.001), age (R = -0.838, p < 0.001) and BMI of the study subjects (R = -0.258, p = 0.001). Age was found to be the only independent determinant of DMCFC elasticity on multiple linear regression analysis (β = -0.837, p < 0.001). The cut-off values for DMCFC elasticity estimated during ROC analysis provided excellent accuracy in distinguishing between women from various age categories, and to a large degree overlapped with the reference intervals defined as ± 2 SD. Conclusions Shear-wave elastography enables quantitative evaluation of facial fat pad elasticity, creating a new frontier in research on age-related processes. The results indicate that elasticity of the DMCFC decreases significantly with age. Tissue elasticity might be an indirect indicator of metabolic and structural properties of facial adipose tissue and its extracellular matrix.

The objective of this study was to confirm the effect of maternal genistein exposure on body weight of male offspring and the metabolic alterations associated with maternal genistein-induced obesity. Pregnant female Sprague-Dawley (SD) rats were supplemented with 300 mg/kg diet of genistein (GEN) or no genistein (CON) throughout pregnancy and lactation. The growth of male offspring was investigated until 12 week age and the mechanism of obesity was studied using metabonomics by ultra performance liquid chromatography and quadrupole time-of-flight (UPLC Q-TOF) MS with electrospray ionization in positive ESI mode (ESI+). Compared with the CON group, body weight, fat pad and food intake of male offspring in GEN group were increased significantly at the age of weeks 10 to 12 (p

Pharmacological studies have suggested hypothalamic phosphodiesterase-3B to mediate leptin and insulin action in regulation of energy homeostasis. Whereas Pde3b-null mice show altered energy homeostasis, it is unknown whether this is due to ablation of Pde3b in the hypothalamus. Thus, to address the functional significance of hypothalamic phosphodiesterase-3B, we used Pde3b flox/flox and Nkx2.1-Cre mice to generate Pde3b Nkx2.1KD mice that showed 50% reduction of phosphodiesterase-3B in the hypothalamus. To determine the effect of partial ablation of phosphodiesterase-3B in the hypothalamus on energy and glucose homeostasis, males and females were subjected to either a low- or high-fat diet for 19–21 weeks. Only female but not male Pde3b Nkx2.1KD mice on the low-fat diet showed increased body weight from 13 weeks onward with increased food intake, decreased fat pad weights and hypoleptinemia. Glucose tolerance was improved in high-fat diet-fed male Pde3b Nkx2.1KD mice in association with decreased phosphoenolpyruvate carboxykinase-1 and glucose-6-phosphatase mRNA levels in the liver. Also, insulin sensitivity was increased in male Pde3b Nkx2.1KD mice on the low-fat diet. Changes in body weight or in glucose homeostasis were not associated with any alteration in hypothalamic proopiomelanocortin, neuropepide Y and agouti-related peptide mRNA levels. These results suggest that partial loss of phosphodiesterase-3B in the hypothalamus produces a sex-specific response in body weight and glucose homeostasis, and support a role, at least in part, for hypothalamic phosphodiesterase-3B in regulation of energy and glucose homeostasis in mice.

Coconut oil has gained in popularity over recent years as a healthy oil due to its potential cardiovascular benefits. Coconut oil contains medium chain triglycerides (MCT) including lauric acid and capric acid that display beneficial properties in human health. Licorice ( Glycyrrhiza uralensis) is used as a sweetener and in traditional Chinese medicine with anti-inflammatory, antimicrobial, and antioxidant activities. This study investigated the in vivo effects of medium chain-triglycerides (MCT)-coconut oil (MCO) and its combination with licorice extract (LE-MCO) on serum lipid profile, hepatic steatosis, and local fat pad proteins in diet-induced obese mice. No liver toxicity was observed in 45% fat diet (HFD)-fed mice orally treated with LE, MCO, and LE-MCO for 12 weeks. Their supplementation reduced HFD-enhanced body weight, blood glucose, and insulin in mice. Plasma levels of both PLTP and LCAT were boosted in LE-MCO-administered mice. Supplementation of LE-MCO diminished plasma levels of TG and TC with concomitant reduction of the LDL-C level and tended to raise blood HDL-C level compared to that of HFD alone-mice. Treatment of LE-MCO encumbered the hepatic induction of hepatosteatosis-related proteins of SREBP2, SREBP1c, FAS, ACC, and CD36 in HFD-fed mice. Substantial suppression of this induction was also observed in the liver of mice treated with MCO. Oral administration of LE-MCO to HFD mice boosted hepatic activation of AMPK and the induction of UCP-1 and FATP1 in brown fat. Conversely, LE-MCO disturbed hepatic PPAR-LXR-RXR signaling in HFD-fed animals and reversed HFD-elevated epididymal PPARγ. Collectively, oral administration of LE-MCO may impede hyperlipidemia and hepatosteatosis through curtailing hepatic lipid synthesis.

“Browning” i. e. the transformation of white adipose tissue into brown-like adipose tissue could induce efficient burning of excess fat reserves via induction of non-shivering thermogenesis. For example, activation of ß3 adrenergic receptors has been show to induce such changes, however, it is still not clear, how long after termination of such a treatment, beneficial effects might be maintained. To address this question, we treated rats s.c. for 2 weeks with the ß3 agonist CL-316,243 at 1 mg/kg and assessed interscapular brown fat and inguinal white fat pads weight, UCP-1 (a marker for the brown-like fat phenotype) using immunohistochemistry and H&E staining, at different intervals after treatment termination.One 1 day after the treatment cessation there was a decrease of inguinal white fat pad weight and increase of interscapular fat pad. This change vanished at 7 days for inguinal pad and at 14 days for interscapular pad. Histological analysis of interscapular pads showed increased UCP-1 staining and brown-like morphology in H&E staining slices at 1 day, but not other time points. In case of inguinal pad there were brown-like features in H&E slices at 1 day and less after 7 days, but absent at 14 days. UCP-1 staining was only detected 1 day after the treatment.In conclusion, the present results indicate that browning-like changes of white fat may be short lasting after treatment termination and could require maintenance treatment of inductor to achieve desired therapeutic effect. This might be a serious shortcoming of potential therapeutic use.