Retroperitoneal Adipose Tissue Research Articles

Citrullus mucosospermus Extract Reduces Weight Gain in Mice Fed a High-Fat Diet.

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1β and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

The use of ultrasonography in the transition period to estimate adipose tissue depots and their association with risk of early postpartum hyperketonemia in Holstein dairy cattle

An elevated prepartum BCS is a risk factor for postpartum hyperketonemia (HYK) and elevated fatty acid (NEFA) concentrations in dairy cattle. The association between different adipose tissue depots, such as subcutaneous (SCAT) as well as visceral adipose tissue (VAT) depots and HYK and elevated NEFA concentrations remains unknown. The objective of this 2-part study was to describe SCAT and VAT depots using ultrasonography during the transition period and to associate them with metabolic markers of negative energy balance in early postpartum dairy cows. Multiparous Holstein cows were enrolled in a prospective observational cohort study with 2 cohorts in subsequent study years (Cohort 1: n = 31; Cohort 2: n = 28). At −6, −4, −2, and 2 wk relative to calving (Cohort 1) or −2 and 2 wk relative to calving (Cohort 2) BCS was determined and cows were examined via transcutaneous ultrasound at 6 locations for prediction of adipose tissue mass in 5 depots: 1) abdominal adipose tissue (AAT), 2) retroperitoneal adipose tissue (RPAT), 3) omental adipose tissue (OMAT), 4) mesenteric adipose tissue (MAT), and 5) subcutaneous adipose tissue (SCAT). Postpartum serum NEFA and BHB concentrations were determined twice weekly from 1 to 14 DIM. Cows were categorized as having HYK or high NEFA concentrations (NEFAH) if ≥1 sample resulted in a BHB ≥1.2 mmol/L or NEFA ≥720 µEq/L, respectively. Critical thresholds associated with HYK or NEFAH for each depot at −2 wk relative to calving and the time of maximum estimated depot size were evaluated using logistic regression and a receiver operator characteristic analysis. Abdominal AT increased from −6 to −2 wk relative to calving in cohort 1 but did not differ from −2 to 2 wk relative to calving. Subcutaneous AT did not change from −6 to −2 wk but decreased from −2 to 2 wk relative to calving in cohort 1 and 2. Omental AT accurately (AUC = 0.77) predicted HYK in cohort 1 but was non-informative for the prediction of HYK in cohort 2 (AUC = 0.49). Predicted AT depots were not informative for the prediction of NEFAH (AUC ≤0.59) in either cohort. Results from this study suggest that AT can be monitored during the transition period using the described technique; however, estimated prepartum AT depots at −2 wk relative to expected calving were inaccurate in distinguishing between postpartum NEFAH and non-NEFAH or HYK and non-HYK.

Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise.

Estrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon. We studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n = 64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography. OVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p ≤ 0.005). OVX reduced maximal running capacity by 17% (p = 0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p = 0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p ≤ 0.024). Our results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.

Pre-Weaning Overfeeding Promotes Prepubertal Obesity and Evokes Sexual Dysfunction in Young Adult Rats

Obesity in early life can contribute to several health issues in adulthood, including diabetes, high blood pressure, and high cholesterol, and these conditions are associated with sexual dysfunction. Here, we hypothesized that pre-weaning overfeeding can have long lasting effects on body fat distribution and erectile function that will be observed in young adult males. On postnatal day (PND 1), Wistar rats were separated into two groups: normal litter (NL) with 10 pups per dam, or small litter (SL) with 3 pups per dam. Male rats (n = 8-10 per group) were then assessed at two different time points: during the prepubertal stage (PND 40) and in adulthood (PND 120). Erectile function was assessed only after sexual maturation (i.e., PND 120). Body weight, retroperitoneal and perigonadal adipose tissue (fat pad weight/100g of the body) were evaluated. Following euthanasia at PND 120, the corpus cavernosum (CC) was removed to perform functional studies using a strip myograph. Contractile and relaxation responses were evaluated by electrical field stimulation (EFS) and concentration-response curves (CRC) to phenylephrine [Phe, 1nM-30μM, millinewton (mN)] or acetylcholine (Ach 1nM-30μM, % relaxation) were performed. At the prepubertal stage, SL rats had higher body weight (NL 149±3 vs. SL 186±5, g, p<0.05), and increased retroperitoneal (NL 0.17±0.01 vs. SL 0.32±0.03, g/100g, p<0.05) and perigonadal (NL 0.38± 0.02 vs. SL 0.45±0.03, g/100g, p<0.05) adipose tissue. At PND 120, SL group presented increased body weight (NL 534.2.7±13 vs. SL 631.6±10, g, p<0.05), retroperitoneal (NL 1.31±0.11 vs. SL 1.82±0.14, g/100g, p<0.05) and perigonadal (NL 1.74±0.10 vs. SL 2.18±0.15, g/100g, p<0.05) adipose tissue when compared with NL group. The CC of SL rats at PND 120 had increased contraction induced by EFS for all frequencies (1 Hz: NL 0.5 ± 0.2 mN vs. SL 0.9 ± 0.2 mN; 4 Hz: NL 1.2 ± 0.3 mN vs. SL 1.8 ± 0.2 mN; 16 Hz: NL 1.9 ± 0.4 mN vs. SL 3 ± 0.4 mN), whereas the relaxation was decreased in SL (1 Hz: NL 0.77 ± 0.18% vs. SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs. SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs. SL 2.39 ± 0.53%). CRC showed increased contractile response to Phe (Emax NL 2.3±0.3 vs. SL 3.8± 0.6, mN, p=0.05) and reduced potency of ACh (pEC50 NL 6.4±0.6 vs. SL 4.9±0.7, mN, p=0.1) in the CC of SL. Incubation with indomethacin (10μM) abolished the differences in the contractile response induced by EFS or Phe between SL and NL, suggesting a heightened inflammatory response. Moreover, the CC of SL rats presented increased expression of Phospho-p44/42 MAPK (NL 0.9±0.25 vs. SL 1.3±0.11, p=0.2). Finally, proteome profiler cytokine array of serum samples from SL animals showed increased circulating levels of cytokines and chemokines associated with obesity, aging, and vascular dysfunction. Together, these data suggest that early prepubertal obesity has long-lasting negative implications on sexual function in young adulthood. National Institutes of Health (NIH); American Heart Association (AHA); Fulbright Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Advanced PamGene Coregulator Interactome Analysis of PPARgamma Reveals that Diet Influences Regulatory Protein Interactions and Signaling Mechanisms

Studies show a strong correlation with type 2 diabetes mellitus (T2DM) in obese patients developing congestive heart failure (CHF) with rosiglitazone treatment. Rosiglitazone, a thiazolidinedione, treats T2DM by improving insulin resistance. Its use has been halted due to a subset of patients developing CHF through unknown mechanisms. Rosiglitazone targets PPARγ, a nuclear receptor highly expressed in adipose tissue and, to a lesser extent, in cardiac tissue. An important mechanism of PPARγ regulation is through coregulators that can alter transcriptional activity through protein-protein interaction to drive PPARγ toward specific pathways. We hypothesized coregulator interaction with PPARγ may regulate its activity differently in adiposity, inducing CHF through adipose-derived peripheral signaling. To address this, we fed 8-week-old C57BL/6 mice a normal chow (NCD) or high-fat (HFD) diet for 16 weeks. Mice were then injected with rosiglitazone every 48 hours for 4 weeks. In NCD and HFD Rosi mice, we found significantly increased heart weights (p-value<0.05) and various weight changes in five adipose depots. To understand the roles of the PPARγ coregulator interactome in adiposity, we used our state-of-the-art PamGene PamStation Nuclear Hormone Receptor chip to measure the interaction of PPARγ with 155 coregulators in five adipose depots and the liver. In adipose depots increasing in weight due to Rosi treatment, such as retroperitoneal white adipose tissue (WAT) and mesenteric WAT, more coregulators associated with the PPARγ complex. Conversely, depots that did not change in weight with Rosi treatment, such as epididymal WAT and inguinal WAT, showed a reduction of coregulators leaving the PPARγ complex, indicating differential PPARγ regulation. Our data suggests that the coregulator interactome of PPARγ in adipose depots represents potential therapeutic targets, and understanding how PPARγ regulation is different in adiposity is crucial to understanding the negative side effects of rosiglitazone treatment. R01DK121797 (T.D.H.) R01DA058933 (T.D.H.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.

Fructooligosaccharides Supplementation: A Good Choice for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease?

Background and objectives: Carbohydrates such as fructooligosaccharides (FOSs) are associated with improved gastrointestinal health and the prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFAs). Methods: Sixty C57BL/6 mice received the following diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed the animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profiles; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; and SCFAs in the feces. Results: Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There were statistical differences found in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Conclusions: Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

Egg white hydrolysate protects white adipose tissue against metabolic insult in deoxycorticosterone acetate-salt rats.

The purpose of this study was to investigate the effect of an egg white hydrolysate (EWH) to protect white adipose tissue damage from cardiometabolic changes induced by severe hypertension. Male Wistar rats were uninephrectomised and divided: SHAM (weekly subcutaneous vehicle (mineral oil + propylene glycol, 1:1)), SHAM + EWH (subcutaneous vehicle plus EWH via gavage, 1 g/kg per day), DOCA (deoxycorticosterone acetate diluted in vehicle subcutaneously weekly in subsequent doses of 20 mg/kg -1st week, 12 mg/kg - 2–3th week, and 6 mg/kg -4–8th week, respectively, plus 1 % NaCl and 0·2 % KCl in drinking water), and DOCA + EWH. Body weight gain, food and water intake, glucose and lipid metabolism were evaluated. Oxidative stress was assessed by biochemical assay and immunofluorescence for NOX-1, nuclear factor kappa B (NFκB), and caspase-3 in retroperitoneal white adipose tissue (rtWAT). Proinflammatory cytokines (IL-6 and 1β), CD163+ macrophage infiltration, and immunohistochemistry for TNFα and uncoupling protein-1 were evaluated, as well as histological analysis on rtWAT. Glutathione peroxidase and reductase were also determined in plasma. EWH showed hypocholesterolemic, antioxidant, anti-inflammatory, and anti-apoptotic properties in the arterial hypertension DOCA-salt model. The results demonstrated the presence of functional changes in adipose tissue function by a decrease in macrophage infiltration and in the fluorescence intensity of NFκB, NOX-1, and caspase-3. A reduction of proinflammatory cytokines and restoration of antioxidant enzymatic activity and mitochondrial oxidative damage by reducing uncoupling protein-1 fluorescence intensity were also observed. EWH could be used as a potential alternative therapeutic strategy in the treatment of cardiometabolic complications associated with malignant secondary arterial hypertension.

(054) Erectile Dysfunction in Young Adulthood as a Consequence of Early Childhood Obesity

Abstract Introduction Childhood obesity is a worrisome health concern for children and teenagers, as it can contribute to several health issues in adulthood, including diabetes, high blood pressure, and high cholesterol. These conditions have been associated with sexual dysfunction. However, the precise impact of early childhood obesity on erectile function in adult males remains uncertain. Objective We hypothesized that overfeeding during early childhood can have lasting effects on body fat distribution, blood pressure, and erectile function in young adult males. Methods On postnatal day (PND 1), Wistar rats were separated into two groups: normal litter (NL) with 10 pups per dam, or small litter (SL) with 3 pups per dam. Male rats (n = 8-10 per group) were then assessed at two different time points: during the prepubertal stage (PND 40) and in adulthood (PND 120). Erectile function was assessed only after sexual maturation (i.e., on PND 120). Body weight, retroperitoneal and perigonadal adipose tissue (fat pad weight/100g of the body) were evaluated. The mean blood pressure (MBP) was recorded in conscious rats using the indirect tail-cuff method. Following euthanasia at PND 120, the corpus cavernosum was removed to perform functional studies using a strip myograph. Contractile and relaxation responses were evaluated by electrical field stimulation (EFS) and concentration-response curves (CRC) to phenylephrine [Phe, 1nM-30μM, millinewton (mN)] or acetylcholine (Ach 1nM-30μM, % relaxation) were performed. Results At the prepubertal stage, SL rats had higher body weight (NL 149±3 vs. SL 186±5, g, p&amp;lt;0.05), and increased retroperitoneal (NL 0.17±0.01 vs. SL 0.32±0.03, g, p&amp;lt;0.05) and perigonadal (NL 0.38± 0.02 vs. SL 0.45±0.03, g, p&amp;lt;0.05) adipose tissue. At PND 120, SL group presented increased body weight (NL 534±13vs. SL 631.6±10, g/100g, p&amp;lt;0.05), retroperitoneal (NL 1.31±0.11vs. SL 1.82±0.14, g/100g, p&amp;lt;0.05) and perigonadal (NL1.74±0.10vs. SL 2.18±0.15, g/100g, p&amp;lt;0.05) adipose tissue when compared with NL group. Moreover, SL rats presented increased MBP (NL 114.9±0.58 vs SL 120.5±1.2, mmHg). The corpus cavernosum of SL rats at PND 120 had increased contraction induced by EFS for all frequencies (1 Hz: NL 0.5 ± 0.2 mN vs SL 0.9 ± 0.2 mN; 4 Hz: NL 1.2 ± 0.3 mN vs SL 1.8 ± 0.2 mN; 16 Hz: NL 1.9 ± 0.4 mN vs SL 3 ± 0.4 mN), whereas the relaxation was decreased (1 Hz: NL 0.77 ± 0.18% vs SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). CRC showed increased contractile response to Phe (Emax NL 2.3±0.3 vs. SL 3.8± 0.6, mN, p=0.05) and reduced potency of ACh (pEC50 NL 6.4±0.6 vs SL 4.9±0.7, mN, p=0.1) in the corpus cavernosum of SL. Incubation with indomethacin (10uM) abolished the differences in the contractile response induced by EFS or Phe between SL and NL, suggesting a heightened inflammatory response. Conclusions These data suggest that early childhood obesity has long-lasting negative implications on sexual function in adulthood. Disclosure No.

Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring's Metabolic Profile in a Swine Model.

Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring's adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring's adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes.

Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.

Abdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity. Female C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated. While limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this 'genetic fingerprint' is important for ovarian metastases to the OFB. In accordance with the 'seed and soil' theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.

Combined supplementation with hesperidin, phytosterols and curcumin decreases adiposity and improves metabolic health in ovariectomized rats.

In recent years many women have looked for alternative therapies to address menopause. Hesperidin, phytosterols and curcumin are bioactive compounds that can ameliorate some cardiovascular risk factors associated with menopause, although there are no data concerning the effects of their combined supplementation. We used ovariectomized (OVX) rats, a postmenopausal model with oestrogen deficiency, to evaluate whether supplementation with a multi-ingredient (MI) including hesperidin, phytosterols and curcumin for 57 days would display beneficial effects against fat mass accretion and metabolic disturbances associated with menopause. Twenty OVX rats were orally supplemented with either MI (OVX-MI) or vehicle (OVX). Furthermore, 10 OVX rats orally received the vehicle along with subcutaneous injections of 17β-oestradiol biweekly (OVX-E2), whereas 10 rats were sham operated and received oral and injected vehicles (control group; SH). MI supplementation partly counteracted the fat mass accretion observed in OVX animals, which was evidenced by decreased total fat mass, adiposity index, the weight of retroperitoneal, inguinal and mesenteric white adipose tissue (MWAT) depots and MWAT adipocyte hypertrophy. These effects were accompanied by a significant decrease in the circulating levels of leptin and the mRNA levels of the fatty acid uptake-related genes Lpl and Cd36 in MWAT. These results were very similar to those observed in OVX-E2 animals. OVX-MI rats also displayed a higher lean body mass, lean/fat mass ratio, adiponectin-to-leptin ratio and insulin sensitivity than their OVX counterparts. Our findings can pave the way for using this MI formulation as an alternative therapy to manage obesity and to improve the cardiometabolic health of menopausal women.

Bilateral adrenal infarction and insufficiency associated with antiphospholipid syndrome and surgery: a case report

BackgroundAntiphospholipid syndrome causes systemic arterial and venous thromboses due to the presence of antiphospholipid antibodies. Adrenal insufficiency is a rare complication of antiphospholipid syndrome that may result in fatal outcomes if left untreated. Therefore, we report adrenal insufficiency as a rare complication of bilateral adrenal infarction associated with antiphospholipid syndrome and trauma surgery.Case presentationA 64-year-old male patient underwent surgery for a left traumatic hemothorax. He concurrently had antiphospholipid syndrome and was receiving warfarin. Postoperatively, the patient complained of severe lumbar back pain despite resuming anticoagulation therapy, and he experienced paralytic ileus and shock. Abdominal contrast-enhanced computed tomography revealed adrenal swelling and increased surrounding retroperitoneal adipose tissue density. Diffusion-weighted abdominal magnetic resonance imaging showed high-intensity areas in the bilateral adrenal glands. Cortisol and adrenocorticotropic hormone levels were 3.30 μg/dL and 185.1 pg/dL, respectively. Subsequently, the patient was diagnosed with bilateral adrenal infarction and acute adrenal insufficiency, and hydrocortisone was immediately administered. Adrenal insufficiency improved gradually, and the patient was discharged after initiating steroid replacement therapy.ConclusionsThe timing of postoperative anticoagulant therapy initiation remains controversial. Therefore, adrenal insufficiency due to adrenal infarction should be monitored while anticoagulant therapy is discontinued in patients with antiphospholipid syndrome.

Effects of Pinealectomy on the Daily Profile of Circadian Clock and Apoptosis Components in Rat Retroperitoneal Adipose Tissue

Effects of Pinealectomy on the Daily Profile of Circadian Clock and Apoptosis Components in Rat Retroperitoneal Adipose Tissue

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI

BackgroundExisting literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PurposeTo implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. Material and methodsMRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). ResultsThe proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. ConclusionConvolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

Liraglutide modulates morpho-functional and inflammatory gastrointestinal responses in rats.

Obesity impairs homeostatic control of energy and is associated with chronic low-grade inflammation. Effects of glucagon-like peptide-1, the target in the gastrointestinal tract for anti-obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity. Twenty-six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 μg (n = 8), or 1200 μg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF-α and TGF-β1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal-Wallis test, followed by Dunn's multiple comparison test. Liraglutide-treated animals had better feeding efficiency and higher caloric intake in a dose-dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High-dose treatment decreased levels of TNF-α and enhanced levels of TGF-β1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases. Liraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity-related outcomes, and such effects seemed to be driven by its action on glucagon-like peptide-1 receptors in the gastrointestinal tract slowing gastric motility.

The clinical value of radical resection of retroperitoneal lipo-lymphatic layer for pancreatic head cancer

Objective: To investigate the clinical value of the novel approach,radical resection of the retroperitoneal lipo-lymphatic layer (RRRLLL),in the surgical treatment of resectable pancreatic head cancer. Methods: Between June 2020 and June 2022,a total of 221 patients with pancreatic head cancer underwent surgical treatment using the RRRLLL approach(RRRLLL group),while 107 patients received traditional surgical treatment(traditional group) in five high-volume pancreatic centers in China. Data from surgical technique and clinical perioperative outcomes,including lymph node harvested,surgical time,and complications,were analyzed. The RRRLLL group consisted of 144 males and 77 females with an age of (67.5±9.0) years(range:41.3 to 81.1 years). The traditional group included 71 males and 36 females,with an age of (66.3±8.1) years(range:45.1 to 79.2 years). Statistical analysis was performed using the K-S test,Z test,or χ2 test. Results: Pancreaticoduodenectomy was performed successfully in all patients,achieving R0 resection. RRRLLL group surgery required mobilization of retroperitoneal adipose and lymphatic tissues starting from the right edge of the inferior vena cava and extending to the left side,up to the superior mesenteric artery,down to the inferior mesenteric artery,and left to the left side of the aorta,including the perineural and lymphatic tissues around the superior mesenteric artery and the sheath of the mesenteric artery. However,the traditional group did not include the areas mentioned above in the scope of clearance. There were no statistically significant differences between the RRRLLL group and the traditional group in terms of age,sex,tumor size,T stage,and vascular invasion (all P>0.05). However,the number of lymph nodes harvested in the RRRLLL group was significantly higher at 28.7±9.0 (range: 18 to 39) compared to 18.2±8.0 (range: 12 to 21) in the traditional group (Z=-10.691,P<0.05). There were no statistically significant differences in the number of positive lymph nodes,N staging,and postoperative complications between the two groups. Conclusion: The RRRLLL approach improved lymph node dissection compared to the traditional approach,potentially leading to reduced recurrence rates.

Differential depot-specific parameters of adipose tissue cellularity and thermogenesis in preobese congenic LA/Ntul//-cp rats

To determine the effects of adipose tissue development during early normal postweaning growth, groups of lean and obese LA/N//tul-cp rats were subjected to measures of caloric intake, linear growth and of adipose tissue mass, cell lipid content, and adipocyte number in principle adipose tissue depots at 6 weeks of age, prior to the expression of significant adiposity. Live body weights and daily caloric intake of obese &gt; lean by 6 weeks of age, but parameters of linear growth were similar in both phenotypes. Resting metabolic rate (RMR) and the thermic response to norepinephrine (NE, 200 µg/KG BW, s.c.) of lean &gt;&gt; obese rats. Adipose tissue mass and combined fat pad mass:body weight ratio of Dorsal Subcutaneous (DOR), Retroperitoneal (RP), Gonadal (GON), and Interscapular brown adipose tissue (IBAT) depots were greater in the obese than lean phenotype, with the greatest magnitude of increase in the DOR subcutaneous depot. Adipocyte number was modestly greater in DOR subcutaneous depot, while adipocyte lipid content was greater in the RP and GON depots of obese but not lean rats. The IBAT mass and proportion of IBAT:body weight of obese &gt;&gt; lean. These results are consistent with the differential onset of adipose tissue depot growth initially occurs via hyperplasia in the dorsal subcutaneous depot and via hypertrophy in the RP and GON abdominal depots, while lean tissue development was of similar magnitude in both phenotypes at this age.

Abstract P382: Long-term Consequences Of Early Childhood Obesity In The Endothelial And Erectile Function Of Male Rats

The consequences of obesity to endothelial and erectile dysfunction are well documented, however, the consequences of obesity in early childhood in later years are unknown. We hypothesize that early childhood obesity induced by postnatal overfeeding impairs aortic reactivity, erectile function, and blood pressure in prepubertal and adult male rats. At postnatal day (PND) 1, Wistar rats were divided into a normal litter (NL, dams were kept with 5 female and 5 male pups) or small litter (SL, dams were kept with 2 male and 1 female pup). The rats were evaluated at two time points prepubertal (PND 40), and in adulthood (PND 120). Body weight (g) and retroperitoneal adipose tissue (fat pad weight/100g of the body n=9-13) were evaluated. The mean blood pressure (MBP, mmHg n=6-7) was measured in conscious rats by indirect tail-cuff method. Aorta and corpus cavernosum were removed. Vascular function was performed via pin myograph and erectile function via strip myograph. Concentration-response curves to phenylephrine (PE) or acetylcholine (ACh) were performed. Prepubertal SL rats had higher body weight (NL 148±2 vs. SL 185±4, g, p&lt;0.05), and adipose tissue deposition (NL 0.17±0.09 vs. SL 0.32±0.03, p&lt;0.05). SL at PND 120 had higher body weight (NL 419±9 vs SL 462±5, g, p&lt;0.05) and retroperitoneal adipose tissue (NL 1.2±0.9 vs SL 1.6±0.1, p&lt;0.05]), and SL rats presented increased MBP (NL 114.9±0.58 vs SL 120.5±1.20). No changes in endothelium-dependent relaxation were observed in the aorta at PND 40 or 120. However, there was an increase in vascular contractility in SL group at PND 40 (Emax: NL 1.17±0.40 vs SL 1.47±0.06, g, p&lt;0.05). In the corpus cavernosum, the relaxation induced by electrical field stimulation was significantly decreased for all frequencies of stimulation in SL rats at PD120 compared to NL rats (1 Hz: NL 0.77 ± 0.18% vs SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). Our data suggest that obesity in early childhood can cause long-lasting vascular damage to males that can be associated with erectile dysfunction in adulthood.

C-phycocyanin extracted from Spirulina using a green solvent approach presents an anti-obesity characteristic in mice fed a hyperlipidic diet

The effects of C-phycocyanin extract, obtained from Spirulina biomass using a sustainable method with water as solvent, on the white adipose tissue of male mice fed a high-fat diet were evaluated. The normolipid diet and C-phycocyanin groups were similar regarding body mass gain, leptin concentration and phosphorylated protein nuclear factor kappa B p-50 subunit expression. The C-phycocyanin group showed a notable reduction in serum resistin (88.18 ± 31.54, normolipid diet 158.5 ± 52.43) (pg/mL) and the concentration of the pro-inflammatory cytokine tumor necrosis factor alpha (p < 0.05) in 16 weeks of treatment within the retroperitoneal white adipose tissue. The high-fat diet has been associated with obesity development, and the utilization of artificial dyes has been linked to adverse effects. However, C-phycocyanin, a natural pigment, demonstrated promising outcomes. Our findings suggest that the C-phycocyanin extract effectively inhibited body mass gain, regulated leptin and resistin levels, and prevented the increase a pro-inflammatory state.