Visceral Fat Accumulation Research Articles

Obesity Pillars Roundtable: Obesity and South Asians

BackgroundCompared to other races/ethnicities, individuals from South Asia with obesity are strikingly susceptible to the presence of CVD risk factors and onset of CVD events – in part due to adiposopathic anatomic and metabolic responses to positive caloric balance. Pathogenic endocrine and immune effects of adipocyte hypertrophy and visceral fat accumulation both directly and indirectly promote among the most common metabolic diseases encountered in clinical practice – many being major cardiovascular disease (CVD) risk factors. This is especially applicable to those from South Asia – largely due to genetics, epigenetics, unhealthful nutrition, and physical inactivity. MethodsThis roundtable discussion included 4 obesity specialists engaged in the clinical management of obesity among patients of South Asian descent. ResultsPatients with obesity from South Asia have increased adipocyte size, fewer (functional) adipocytes, and increased visceral adiposity accompanied by functional endocrine and immune abnormalities. This helps explain the increased CVD risk factors and increased CVD risk among this unique population. These CVD risk factors include increased prevalence of metabolic syndrome (even at lower body mass index relative to other races), insulin resistance, type 2 diabetes mellitus, increased lipoprotein (a), and adiposopathic dyslipidemia [(i.e., elevated triglyceride levels, reduced high density lipoprotein cholesterol levels, increased low density lipoprotein (LDL) particle number, and increased prevalence of smaller and denser LDL particles]. ConclusionThe four panelists of this roundtable discussion describe their practical diagnostic processes and treatment plans for patients from South Asia, with an emphasis on a patient-centered approach to obesity in this unique population.

Genomic Analysis of Visceral Fat Accumulation in Holstein Cows.

Visceral fat is related to important metabolic processes, including insulin sensitivity and lipid mobilization. The goal of this study was to identify individual genes, pathways, and molecular processes implicated in visceral fat deposition in dairy cows. Data from 172 genotyped Holstein cows classified at slaughterhouse as having low (n = 77; omental fold 5 mm in thickness and minimum fat deposition in omentum) or high (n = 95; omental fold 20 mm in thickness and marked fat deposition in omentum) omental fat were analyzed. The identification of regions with significant additive and non-additive genetic effects was performed using a two-step mixed model-based approach. Genomic scans were followed by gene-set analyses in order to reveal the genetic mechanisms controlling abdominal obesity. The association mapping revealed four regions located on BTA19, BTA20 and BTA24 with significant additive effects. These regions harbor genes, such as SMAD7, ANKRD55, and the HOXB family, that are implicated in lipolysis and insulin tolerance. Three regions located on BTA1, BTA13, and BTA24 showed marked non-additive effects. These regions harbor genes MRAP, MIS18A, PRNP and TSHZ1, that are directly implicated in adipocyte differentiation, lipid metabolism, and insulin sensitivity. The gene-set analysis revealed functional terms related to cell arrangement, cell metabolism, cell proliferation, cell signaling, immune response, lipid metabolism, and membrane permeability, among other functions. We further evaluated the genetic link between visceral fat and two metabolic disorders, ketosis, and displaced abomasum. For this, we analyzed 28k records of incidence of metabolic disorders from 14k cows across lactations using a single-step genomic BLUP approach. Notably, the region on BTA20 significantly associated with visceral fat deposition was also associated with the incidence of displaced abomasum. Overall, our findings suggest that visceral fat deposition in dairy cows is controlled by both additive and non-additive effects. We detected at least one region with marked pleiotropic effects affecting both visceral fat accumulation and displaced abomasum.

In response to the article "The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors". Pol J Radiol 2020; 85: e62-e66.

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Aggarwal A, Bagri N. In response to the article “The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors”. Pol J Radiol 2020; 85: e62-e66. Polish Journal of Radiology. 2022;87(1):232-232. doi:10.5114/pjr.2022.115807. APA Aggarwal, A., & Bagri, N. (2022). In response to the article “The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors”. Pol J Radiol 2020; 85: e62-e66. Polish Journal of Radiology, 87(1), 232-232. https://doi.org/10.5114/pjr.2022.115807 Chicago Aggarwal, Ankita, and Neha Bagri. 2022. "In response to the article “The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors”. Pol J Radiol 2020; 85: e62-e66". Polish Journal of Radiology 87 (1): 232-232. doi:10.5114/pjr.2022.115807. Harvard Aggarwal, A., and Bagri, N. (2022). In response to the article “The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors”. Pol J Radiol 2020; 85: e62-e66. Polish Journal of Radiology, 87(1), pp.232-232. https://doi.org/10.5114/pjr.2022.115807 MLA Aggarwal, Ankita et al. "In response to the article “The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors”. Pol J Radiol 2020; 85: e62-e66." Polish Journal of Radiology, vol. 87, no. 1, 2022, pp. 232-232. doi:10.5114/pjr.2022.115807. Vancouver Aggarwal A, Bagri N. In response to the article “The relationship between renal sinus lipomatosis detected at abdominal computed tomography and abdominal visceral and subcutaneous fat accumulation and metabolic risk factors”. Pol J Radiol 2020; 85: e62-e66. Polish Journal of Radiology. 2022;87(1):232-232. doi:10.5114/pjr.2022.115807.

Calorie restriction on normal body weight mice prevents body weight regain on a follow-up high-fat diet by shaping an obesity-resistant-like gut microbiota profile.

Calorie restriction (CR) is one of the most common approaches for obesity treatment, but whether resuming ad libitum feeding after CR in normal-weight mice can affect excessive weight regain remains poorly studied. To address this issue, male C57BL/6 mice were placed in three groups: a control group (n = 10), a group fed normal diet with 30% CR (n = 20); and a group fed a HF diet (n = 30). After four weeks, the CR group was fed either a normal diet (NDCR, n = 10) or a high-fat diet (HFCR, n = 10) for an additional eight weeks. At the end of the experiment, mice in the HF group ranked in the upper and lower thirds for weight gain were designated as obesity-prone (HFOP, n = 10) and obesity-resistant (HFOR, n = 10), respectively. CR delayed weight regain and visceral fat accumulation. Gut microbiota in the HFCR group were more similar to the HFOR group than the HFOP group, mainly due to reversion of the decreased level of Clostridiales induced by CR. Mediation analysis showed that Clostridiales may delay body weight regain by affecting the interconversion of succinate and fumarate. Random forest and structural equation analyses showed Christensenellaceae were the most important biomarker for alleviation of obesity. In conclusion, CR shapes an obesity-resistant-like gut microbiota profile that may attenuate body weight regain.

Lipid ratios and obesity indices are effective predictors of metabolic syndrome in women with polycystic ovary syndrome.

Background:Insulin resistance (IR) is common in women with polycystic ovary syndrome (PCOS). Metabolic syndrome (MS) involves IR, arterial hypertension, dyslipidemia, and visceral fat accumulation. Therefore, fatness indices and blood lipid ratios can be considered as screening markers for MS. Our study aimed to evaluate the predictive potential of selected indirect metabolic risk parameters to identify MS in PCOS.Methods:This cross-sectional study involved 596 women aged 18–40 years, including 404 PCOS patients diagnosed according to the Rotterdam criteria and 192 eumenorrheic controls (CON). Anthropometric and blood pressure measurements were taken, and blood samples were collected to assess glucose metabolism, lipid parameters, and selected hormone levels. Body mass index (BMI), waist-to-height ratio (WHtR), homeostasis model assessment for insulin resistance index (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides-to-HDL cholesterol ratio (TG/HDL-C) were calculated. MS was assessed using the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria.Results:MS prevalence was significantly higher in PCOS versus CON. Patients with both MS and PCOS had more unfavorable anthropometric, hormonal, and metabolic profiles versus those with neither MS nor PCOS and versus CON with MS. LAP, TG/HDL-C, VAI, and WHtR were the best markers and strongest indicators of MS in PCOS, and their cut-off values could be useful for early MS detection. MS risk in PCOS increased with elevated levels of these markers and was the highest when TG/HDL-C was used.Conclusions:LAP, TG/HDL-C, VAI, and WHtR are representative markers for MS assessment in PCOS. Their predictive power makes them excellent screening tools for internists and enables acquiring accurate diagnoses using fewer MS markers.

Sick fat (adiposopathy) as the main contributor to metabolic syndrome

Obesity, primarily the accumulation of visceral fat (prone to lipolysis and inflammation) is considered the most important pathogenetic link in insulin resistance, metabolic syndrome and type 2 diabetes mellitus. The purpose of the review was to present and summarize current information on the negative impact of adipose tissue dysfunction and the role of this phenomenon in the pathogenesis of the metabolic syndrome and type 2 diabetes mellitus. Material and methods. A systematic search of Web of Science, EMBASE, MEDLINE, and Google Scholar databases was performed. Results. Adipose tissue secretes a huge variety of biologically active substances - free fatty acids, adipokines, inflammatory mediators. These substances have a negative effect on insulin-sensitive and all other tissues, inducing inextricably linked freeradical oxidation, mitochondrial dysfunction, histotoxic hypoxia, maladaptive autophagy, apoptosis, dysregulation of transcriptome and post-translational processes, overload of non-fat tissues with lipids (lipotoxicity) enhanced by hyperinsulinemia, and many other cytotoxic mechanisms. Target organ damage disrupts the finely tuned network of feedbacks between the brain, liver, gut, microbiome, muscles, adipose tissue, classic glands and the rest of the organs, provided by myokines, hepatokines, bathokines and other substances, among others. Based on some experimental and clinical data, we agree with the notions that the qualitative aspect - adipocyte dysfunction (adiposopathy) - is at least as important as cell mass. Sick fat has a number of differences from healthy tissue, among which there are indicated mitochondrial dysfunction, inflammation, disorders of browning, cell death, and removal of senescent cells (senolysis). The obesity paradox can be explained from the pathophysiological point of view by this distinction (although the main explanation, in our opinion, should be sought in the internal validity of the works revealing this phenomenon). Conclusion. The treatment of obesity and its consequences should be based on «healing» rather than «extermination» of adipocytes. Implementation of this approach requires homeostatic influence on neuroimmunoendocrine regulation. Of the available tools, metformin, incretin drugs, sodium-glucose transporter inhibitors, and bariatric surgery probably meet this requirement the most.

An attempt to assess visceral fat accumulation by measuring fat content in the hepato-renal gap on abdominal ultrasound

目的：生活習慣病と内臓肥満の重複が動脈硬化を進展させ，そのリスクを高めると言われている．内臓脂肪蓄積の評価にはCT検査（以下Fat scan）での評価が一般的である．しかし，放射線の被曝，コスト面で健診などの多人数に施行するのは難しい．一方，超音波検査は被曝の問題もなく簡便な方法で内臓脂肪蓄積の様々な報告がなされている．今回，腹部超音波検査の肝腎間隙脂肪層（以下perirenal fat；PRF）に着目し検討を行った．対象と方法：対象は2018年に人間ドックを受診し，腹部超音波検査とFat Scanを施行した478名（男333名，女145名，平均年齢58.3±11.7歳，平均BMI24.6±3.2）．腹部超音波検査の肝腎画像からPRFを計測しFat scanと比較検討した．また，問診票から内臓脂肪蓄積の関係について検討した．結果と考察：全対象者の平均は腹部超音波検査のPRFで5±5.5（1‐7 中央値3）mm，Fat scanでの内臓脂肪面積は110±51 cm2となった．腹部超音波検査のPRFとFat scanとの相関関係は0.66（p値<0.001）と正の相関を認めた．Fat scanで測定した内臓脂肪蓄積とされる100 cm2をカットオフとし，腹部超音波検査のPRFとROC解析を行うと閾値は3 mmとなった．AUC：0.855（95％CI0.821‐0.889），感度81％，特異度81％，および陽性的中率80％，陰性的中率82％であった．超音波検査で肝腎間隙脂肪層が3 mm以上あれば内臓脂肪蓄積100 cm2以上を推測できると考えられた．結論：腹部超音波検査でPRFを計測することで，健康診断やスクリーニング検査で内臓脂肪蓄積を推測でき診断の一助になる.

Combination of somatosensory stimulation and diet with a reduced glycemic index in preventing and correcting of obesity

To prevent and correct the accumulation of excess fat mass, especially visceral adipose tissue, a combination of somatosensory stimulation in the form of reflex massage with the use of a diet with a low glycemic index was used. Changes in anthropometric parameters, lipid profile, and increase in atherogenic coefficient depending on body mass index were revealed. The organization and implementation of a preventive and health improvement program based on a combination of somatosensory stimulation and a diet with a low glycemic index allows the correction of the lipid profile, reducing the severity of visceral fat accumulation.

Renin-angiotensin system modulation through enalapril and/or exercise training improves visceral adiposity in obese mice

IntroductionObesity-related metabolic diseases occur as a result of disruptions in white adipose tissue (WAT) plasticity, especially through visceral fat accumulation and adipocyte hypertrophy. This study aimed to evaluate the impact of renin–angiotensin system (RAS) and bradykinin receptors modulation by enalapril treatment and/or exercise training on WAT morphology and related deleterious outcomes. MethodsMale C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At the 8th week, HF-fed animals were divided into sedentary (HF), enalapril treatment (HF-E), exercise training (HF-T), and enalapril treatment plus exercise training (HF-ET) groups. Following the experimental protocol, body mass gain, adiposity index, insulin resistance, visceral WAT morphometry, renin-angiotensin system, and bradykinin receptors were evaluated. ResultsThe HF group displayed increased adiposity, larger visceral fat mass, and adipocyte hypertrophy, which was accompanied by insulin resistance, overactivation of Ang II/AT1R arm, and favoring of B1R in bradykinin receptors profile. All interventions ameliorated visceral adiposity and related outcomes by favoring the Ang 1–7/MasR arm and the B2R expression in B1R/B2R ratio. However, combined therapy additively reduced Ang II/Ang 1–7 ratio. ConclusionOur results suggest that Ang 1–7/MasR arm and B2R activation might be relevant targets in the treatment of visceral obesity.

Study of Platelet Indices in Patients with Metabolic Syndromes: A Study Protocol

Background: Metabolic syndrome is a syndrome of unified metabolic disorder which includes abdominal obesity (AO), hypertension, hypertriglyceridemia (HTG), hyperglycemia and decreased high-density lipoprotein (HDL). Metabolic syndrome subjects are exposed to greater chances to have insulin resistance, visceral fat accumulation, atherogenic changes to the vessels, abnormal lipid levels and abnormal functioning of endothelium. Platelets play a key role in hemostasis. The mean platelet volume (MPV) and platelet’s proportion are indicators of platelet function. This study aims to find the correlation between various platelet indices in patients with Metabolic syndromes.&#x0D; Methods: This prospective study is planned to be conducted in AVBRH, Wardha. Patients anthropometric parameters like height, weight, blood pressure, waist circumference, hip circumference and biochemical parameters such as fasting blood glucose, serum triglycerides, serum HDL, and mean platelet volumes will be assessed. Total 130 subjects will be assessed and data will be analyzed to estimate a correlation between platelet indices and metabolic syndromes.&#x0D; Expected Results: A significant correlation is expected between various platelet indices in patients of different metabolic syndromes.

MXD3 Promotes Obesity and the Androgen Receptor Signaling Pathway in Gender-Disparity Hepatocarcinogenesis.

Obesity is closely linked to metabolic diseases, particularly non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD), ultimately leading to hepatocellular carcinoma (HCC). However, the molecular mechanisms of NASH-associated HCC (NAHCC) remain elusive. To explore the impact of Max dimerization protein 3 (MXD3), a transcription factor that regulates several cellular functions in disorders associated with metabolic diseases, we conditionally expressed Mxd3 proteins using Tet-on mxd3 transgenic zebrafish (MXs) with doxycycline (MXs + Dox) or without doxycycline (MXs − Dox) treatment. Overexpression of global MXD3 (gMX) or hepatic Mxd3 (hMX) was associated with obesity-related NAFLD pathophysiology in gMX + Dox, and liver fibrosis and HCC in hMX + Dox. Oil Red O (ORO)-stained signals were seen in intravascular blood vessels and liver buds of larval gMX + Dox, indicating that Mxd3 functionally promotes lipogenesis. The gMX + Dox-treated young adults exhibited an increase in body weight and visceral fat accumulation. The hMX + Dox-treated young adults showed normal body characteristics but exhibited liver steatosis and NASH-like phenotypes. Subsequently, steatohepatitis, liver fibrosis, and NAHCC were found in 6-month-old gMX + Dox adults compared with gMX − Dox adults at the same stage. Overexpression of Mxd3 also enhanced AR expression accompanied by the increase of AR-signaling pathways resulting in hepatocarcinogenesis in males. Our results demonstrate that global actions of Mxd3 are central to the initiation of obesity in the gMX zebrafish through their effects on adipogenesis and that MXD3 could serve as a therapeutic target for obesity-associated liver diseases.

Extracellular lipidome change by an SGLT2 inhibitor, luseogliflozin, contributes to prevent skeletal muscle atrophy in db/db mice.

BackgroundDiabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy.MethodsEight‐week‐old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed.ResultsAdministration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P < 0.0001) and sera (P = 0.009). Finally, the accumulation of transcripts associated with fatty acid metabolism, such as Scd1, Fasn, and Elovl6, and of muscle atrophy‐associated transcripts, such as Foxo1, Mstn, Trim63, and Fbxo32, decreased following SGLT2i administration.ConclusionsIntramuscular fatty acid metabolism and gene expression were influenced by the extracellular lipidome, which was modified by SGLT2i. Hence, secondary effects, other than the hypoglycaemic effects of SGLT2i, might lead to the alleviation of sarcopenia.

Comparison of novel visceral obesity indexes with traditional obesity measurements in predicting of metabolically unhealthy nonobese phenotype in hemodialysis patients

BackgroundNormal-weight maintenance hemodialysis (MHD) patients with abdominal obesity exhibited a more proatherogenic profile than overweight and obesity patients with abdominal obesity, highlighting the importance of early identification of metabolically unhealthy nonobese (MUNO) in this population. Visceral fat accumulation plays a crucial role in the development of MUNO. Lipid accumulation product (LAP), visceral adiposity index (VAI) have been proved as reliable visceral obesity markers. The Chinese visceral adiposity index (CVAI) and a body shape index (ABSI) are newly discovered indexes of visceral obesity and have been reported to be associated with multiple metabolic disorders. There are limited studies investigating the associations between different visceral obesity indices and risk of MUNO, especially in hemodialysis patients. Moreover, no general agreement has been reached to date regarding which of these obesity indices performs best in identifying MUNO. We aimed to investigate the prevalence of MUNO in MHD patients and compare the associations between different adiposity indices (CVAI, ABSI,VAI, LAP, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHtR)) with MUNO risk in this population.MethodsWe conducted a multi-center cross-sectional study in Guizhou Province, Southwest China. 1302 nonobese adult MHD patients were included in our study. MUNO was defined as being nonobese and having the presence of > = 2 components of metabolic syndrome (MetS). Nonobese was defined as BMI less than 25 kg/m2. VAI, LAP, CVAI, ABSI, BMI, WC and WHtR were calculated. Logistic regression analyses and receiver operator curve (ROC) analyses were performed.Results65.6% participants were metabolically unhealthy. The ROC curve analysis demonstrated that of the seven obesity indices tested, the VAI (AUC 0.84 for women and 0.79 for men) followed by LAP (AUC 0.78 for women and 0.72 for men) had the highest diagnostic accuracy for MUNO phenotype while ABSI exhibited the lowest AUC value for identifying MUNO phenotypeConclusionsMetabolically unhealthy is highly prevalent in nonobese MHD patients. VAI and LAP outperformed CVAI in discriminating MUNO in MHD patients. Though ABSI could be a weak predictor of MUNO, it is not better than WHtR, WC and BMI.

Effects of menopause on cognitive deficits in a mouse model of metabolic disease.

By 2025, it is estimated that nearly 20% of the U.S. population will be post-menopausal women. Menopause accelerates metabolic disease, a major mid-life risk factor for dementia. Indeed, ∼80% of those with dementia have concurrent metabolic disease and nearly all women with dementia are post-menopausal. We hypothesize that menopause will exacerbate the metabolic and cognitive effects of a high fat diet. Using young-adult and middle-aged C57BL/6J female mice (N= 9-15/group), we modeled metabolic disease via chronic administration of high fat (HF; 60%) diet vs. low fat (LF; 10% fat) control diet. We modeled menopause via daily injections of 4-vinylcyclohexene diepoxide (VCD), which results in accelerated ovarian failure vs. vehicle. To confirm menopause, we performed daily vaginal cytology. We performed a glucose tolerance test (GTT) at 2.5 months and 7 months on the diet. We assessed deficits in spatial memory (object place recognition test) and episodic-like memory (novel object recognition test). There was a main effect of menopause in increasing glucose intolerance, and % weight gain. Longer time in menopause was associated with greater visceral fat accumulation in HF-fed mice. Spatial memory and episodic-like memory were impaired by age, high fat diet, and menopause. The spatial memory deficits were worse in middle-aged menopausal mice compared to the young menopausal mice. Our data show that post-menopausal mice have greater metabolic impairment than pre-menopausal mice, regardless of age. However, deficits in spatial memory due to HF diet or menopause increase with age. This is in line with clinical data showing that post-menopausal women are more susceptible to metabolic disease and are at increased risk for cognitive impairment and dementia. Altogether, our data highlight the importance of considering endocrine age distinctly from chronological age in studies of dementia.

Effects of Milkfat on the Gut Microbiome of Patients After Bariatric Surgery, a Pilot Study.

BackgroundThe efficacy of bariatric surgery may be in part attributed to altered metabolism via new gut microbiome. Milkfat may promote the growth of microbes that are beneficial in long-term weight loss. Understanding the specific gut microbiome changes after surgery and their relationship to milkfat consumption may yield important strategies for managing obesity after bariatric procedures.MethodsIn this pilot study, stool samples were collected from nine patients before and at the time of surgery, and at 1, 3, and 6 months post-surgery. At each time-point, dairy consumption was determined from dietary surveys. 16 s rRNA gene sequencing was performed followed by alpha diversity analysis. Comparisons of relative abundances of microbial taxa and analyses of fatty acids changes were performed.ResultsBariatric surgery led to enrichment of (i) Roseburia, associated with weight loss and (ii) Christensenellaceae, inversely related to body mass index. High milk-fat consumption correlated with enrichment of Blautia, inversely associated with visceral fat accumulation. Faecalibacterium, possibly associated with obesity, increased in patients with low milk-fat consumption. Butter was associated with decreased alpha diversity in all subjects (p-value = 0.038) and the frequency of its use was associated with decreased alpha diversity in patients (correlation = − 0.68, p-value = 0.042). Low-milk-fat consumers showed higher concentration of saturated fatty acids.ConclusionsOur results suggest that incorporating dairy products in post-bariatric-surgery dietary plans may help cultivate a gut microbiome that is effective in regulating fat storage as well as digesting beneficial metabolites. These observations will be helpful for the management of obesity in general population as well.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11695-021-05805-z.

Abstract 12815: Changes in Circulating microRNA-375 Levels in Response to Lifestyle Interventions and Improvements in Visceral Adiposity and Hepatic Fat Content: The CENTRAL Trial

Introduction: MicroRNA (miRNAs) are short non-coding RNAs that regulate gene expression at the translational level. Circulating exosomal miRNAs have emerged as novel biomarkers of obesity, insulin resistance, and related metabolic abnormalities. miR-375 has been identified as a regulator of insulin secretion, and miR-375 may also be involved in regulating visceral adiposity and ectopic fat accumulation in the liver. Hypothesis: We aimed to investigate whether changes in circulating miR-375 induced by lifestyle interventions were related to improved visceral adiposity and hepatic fat depot among individuals with abdominal obesity. Methods: This study included adults with abdominal obesity from an 18-month diet and physical activity intervention study (the CENTRAL trial) and with available data on circulating miR-375-3p at baseline (n=222) and 18 months (n=152). Magnetic resonance imaging (MRI) was performed to assess body fat distribution and ectopic fat depots. Outcome measurements included 18-month changes in abdominal (total [TAT], visceral [VAT], deep subcutaneous [DSAT], superficial subcutaneous [SSAT]) adipose tissue area and intrahepatic fat content. Results: At baseline, higher levels of miR-375 were related to lower degrees of BMI ( p =0.0006), waist circumference ( p =0.0008), as well as abdominal adipose tissue area (TAT [ p =0.0024], VAT [ p =0.059], DSAT [ p =0.011], and SSAT [ p =0.0027]). There was a significant increase in circulating miR-375 levels after the 18-month lifestyle interventions ( P by paired t-test &lt; 0.0001). When we analyzed effects (β) of per 1 SD increase in miR-375 changes on the outcomes after adjusting for covariates including baseline levels of miR-375 and BMI, we found that greater increase in miR-375 was associated with larger reductions of VAT (β -8.09 [3.09] cm 2 , p =0.01), as well as DSAT (β -7.87 [2.21] cm 2 , p =0.001) and intrahepatic fat content (β -1.38% [0.5%], p =0.006) at 18 months. Conclusions: Circulating miR-375 levels significantly increased after the long-term lifestyle interventions, and greater increases in miR-375 were related to significant improvements in visceral adiposity and liver fat content that are closely related to insulin resistance in adults with abdominal obesity.

Abstract 12419: Internalized Weight Stigma Linked to Greater Visceral Adiposity for Women, but Not Men

Introduction: As visceral adipose tissue (VAT) is an important predictor of CVD risk, it is necessary to understand psychosocial factors possibly related to VAT accrual. Weight stigma is a chronic stressor which particularly impacts women and is associated with increased cortisol secretion. Given that chronically elevated cortisol is linked to VAT increase, weight stigma may lead to accumulation of visceral fat. This study investigated relationships between internalized weight stigma (IWS), VAT, and gender. Hypothesis: We hypothesized that IWS would be positively associated with VAT, and that this relationship would be moderated by gender. We predicted that the relationship between IWS and VAT would be stronger for women than for men. Methods: Participants ( N =70, 81% white, 53% women, M age =30.4±7.8 years, M BMI =28.7±5.5 kg/m 2 , M BF% =32.4±8.9%) completed in-lab measures of demographic factors (age, gender, race/ethnicity), IWS (Weight Bias Internalization Scale-Modified; WBIS-M) and visceral adiposity. VAT mass (g) was measured via DXA scan (Hologic Horizon A DXA system). Primary moderation analysis investigated the effect of gender on associations between IWS and VAT mass. Covariates were age, race/ethnicity, and total BF%. Results: Participants represented a broad range of total BF% (15-48%) and BMI (19.6-45.2 kg/m 2 ). Women displayed greater WBIS-M scores ( M =3.5, SE =0.2) than men ( M =2.7, SE =0.2; p &lt;.01). Differences between VAT mass (g) for women ( M =429.4, SE =39.7) and men ( M =480.1, SE =30.5) were non-significant ( p =.32). After adjusting for covariates in the primary moderation analysis, WBIS-M scores displayed a positive association with VAT mass ( b =31.5, p =.03). The relationship between WBIS-M scores and VAT mass was moderated by gender ( b =74.7, p =.01); no relationship between WBIS-M scores and VAT mass was observed in men ( b =-8.0, p =.68), whereas a positive association between WBIS-M scores and VAT mass was observed in women ( b =66.7, p &lt;.01). Conclusions: Internalization of weight stigma was associated with greater visceral adiposity in women across the BMI spectrum, implicating it as a chronic stressor. Future studies should investigate directionality and causality of this relationship to mitigate stigma-associated CVD risk.

Effects of lighting patterns in pubertal development and metabolism of female wistar rats

Modern lifestyle is characterized by constant exposure to artificial light, which is associated with alterations in biological rhythms, abnormalities to reproductive cycles and metabolic changes. In this study, we aimed to evaluate the effects of four different lighting patterns on puberty timing and on possible metabolic changes in female Wistar rats. Additionally, we developed a machine learning algorithm to automatically classify the stages of the estrous cycle. Adult Wistar rats mated during a week at a photoperiod station where they were exposed to combined red-green-blue lights (RGB) during the photoperiod that varied its spectral composition (i.e., variable color temperature) during the day (RGB-v; N = 14), RGB during the photoperiod with a fixed light color temperature (RGB-f; N = 13) during the whole photoperiod; constant darkness (DD; N = 13) and constant fixed light (LL; N = 15). Experiments were performed only on female litters from postnatal day (PND) 22 to 50. Body weight, puberty onset, estrous cyclicity and serum metabolic parameters were measured. We also collected pictures of vaginal smears to create a dataset of 15,936 images to construct an automatic classifier based on convolutional neural networks. No significant differences were found in the age of vaginal opening; however, the RGB-v group showed a significantly lower number of complete and consecutives cycles. Also, the RGB-f group showed the first complete estrous cycle significantly earlier than the RGB-v group. Female rats housed in LL condition presented significantly lower mean body weight from PND 33 to PDN 47 compared to the other groups. Furthermore, higher levels of plasma triglycerides were found in the DD group compared to RGB-f and RGB-v. HDL levels were significantly lower in RGB-v compared to RGB-f and LL groups. Total cholesterol was significantly lower in RGB-v compared to all groups. Visceral fat was significantly higher in RGB-f compared to the LL group. These results suggest that both changes in photoperiod and lighting quality affect pubertal development and alter lipid profiles and visceral fat accumulation.

Icariin ameliorates metabolic syndrome-induced benign prostatic hyperplasia in rats

Metabolic syndrome (MetS) is an immense health issue that causes serious complications in aging males including BPH. Icariin (ICA) is a flavonol glycoside that exerts a plethora of pharmacological effects. The present investigation tested the potential of ICA to ameliorate benign prostatic hyperplasia (BPH) induced by MetS in rats. Animals were allocated to 5 groups in which the first and second groups were kept on water and regular food pellets. MetS was induced in the third, fourth, and fifth groups by keeping the animals on high fructose and salt diets for twelve consecutive weeks. These groups were given vehicle, ICA (25 mg/kg), and ICA (50 mg/kg), respectively. MetS was confirmed by an increase in rats' weight, accumulation of visceral fat, insulin resistance, and dyslipidemia. This was accompanied by manifestation of BPH including increased prostate weight, prostate index, and histopathological alterations. Treating the animals with both doses of ICA significantly ameliorated the increase in weight and index of the prostate as well as altered prostate histopathology. In addition, ICA significantly decreased cyclin D1 expression, upregulated Bax, and downregulated Bcl2 mRNA expression. ICA prevented lipid peroxidation, reduced glutathione depletion, and catalase exhaustion, which further lowered markers of prostate inflammation such as interleukin-6 and tumor necrosis factor-α. Moreover, ICA prevented the decrease in prostate content of phosphorylated 5'-adenosine monophosphate (AMP)-activated protein kinase (pAMPK). In conclusion, ICA protects against MetS-induced BPH. This is due to its antiproliferative, proapoptotic, antioxidant, and anti-inflammatory activities as well as the activation of AMPK.

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity.

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis.