Metabolic Activity Of Adipose Tissue Research Articles

MDPAO1 peptide from human milk enhances brown adipose tissue thermogenesis and mitigates obesity.

The regulatory effect of breastfeeding on offspring metabolism has garnered significant attention as an effective strategy in combating childhood obesity. However, the underlying mechanism remains largely unknown. Through integrated analysis of multiple human milk peptide databases and functional screening, MDPAO1 (milk-derived peptide associated with obesity 1) was identified as having potential activity in promoting the expression of thermogenic genes. In lactating mice, intervention with MDPAO1 enhanced the thermogenic phenotype of brown adipose tissue (BAT) and overall metabolic activity. Moreover, MDPAO1 intervention led to reduced body weight gain, increased brown fat mass, and improved glucose tolerance and insulin sensitivity in a mouse model of high-fat diet (HFD)-induced obesity. RNA-seq analysis of BAT post-MDPAO1 intervention revealed close association with mitochondrial oxidative respiratory chain and mitophagy. Subsequent in vitro experiments conducted on primary brown adipocytes confirmed that MDPAO1 inhibited mitophagy, increased mitochondrial mass, and elevated levels of mitochondrial respiratory chain complexes. In conclusion, this study underscores the potential of MDPAO1, a peptide enriched in breast milk, in activating the thermogenic phenotype of brown adipose tissue and mitigating obesity, thus offering novel insights into the mechanisms underlying breastfeeding's role in preventing childhood obesity.

GLP-1 therapy increases visceral adipose tissue metabolic activity: lessons from a randomized controlled trial in obstructive sleep apnea.

Glucagon-like peptide-1 (GLP-1) analogues are currently the most widely used pharmacotherapies for weight loss. Their primary mechanism of action is attributed to reduction in energy intake. Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans. Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed to evaluate VAT metabolic activity, expressed as VAT target to background ratio. Treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target to background ratio. There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss. These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation.

Subcutaneous adipose tissue radiodensity: An emerging risk factor for severe COVID-19

BackgroundAdipose tissue radiodensity and metabolic activity may influence COVID-19 outcomes. This study evaluated the association between adipose tissue characteristics and clinical outcomes in COVID-19 patients. MethodsTwo retrospective cohorts of hospitalized COVID-19 patients were analyzed. Subcutaneous adipose tissue radiodensity (SATR) and visceral adipose tissue radiodensity were assessed by computed tomography. Fluorine-18-labelled fluorodeoxyglucose PET/computed tomography measured adipose tissue metabolic activity. Associations with mortality, length of stay, ventilation requirement, and complications were examined using regression analyses. ResultsHigh SATR was independently associated with increased mortality risk (OR: 2.70; P = 0.033), longer hospitalization (P < 0.001), higher rates of mechanical ventilation (P = 0.007), and complications: acute kidney injury (P = 0.001), secondary infection (P = 0.007), shock (P = 0.010), and pulmonary embolism (P = 0.011). SATR positively correlated with SAT glucose uptake (ρ = 0.52) and negatively with leptin levels (ρ = –0.48). ConclusionsElevated SATR at COVID-19 diagnosis predicts disease severity and worse outcomes. SATR is a potential prognostic biomarker for acute and chronic inflammatory conditions.

Potential role of short-chain fatty acids in irritable bowel syndrome in overweight and obese individuals

Due to increasing prevalence of functional diseases of the colon in obese patients, the mechanisms by which the intestinal microbiota affects the development of symptoms of irritable bowel syndrome (IBS) in the setting of metabolic activity of adipose tissue should be investigated. The quantitative and qualitative changes in the pool of synthesized short-chain fatty acids, which have a multidirectional impact on the colonic motility is one of the key mechanisms by which the intestinal microbiota affects the occurrence and features of the course of irritable bowel syndrome. But as regards the issue of whether individual short-chain fatty acids have an impact on the severity of abdominal pain and characteristics of colonic motility dysfunction, it remains a subject of discussions. The study of the mechanisms of impact of short-chain fatty acids on the development and progression of obesity deserves special attention. Increased serum and faecal short-chain fatty acid levels in obese patients can either be a result of changes in the intestinal microflora composition associated with special eating habits and lifestyle, or have an independent effect on the development of obesity in individuals due to intestinal microflora composition disorders that have been already developed. Due to special features of the course of irritable bowel syndrome associated with overweight and obesity, studying the intestinal microbiota composition and the short-chain fatty acids produced by it in this cohort of IBS patients is of particular interest. This publication has been prepared to describe and systematize the possible mechanisms of impact of short-chain fatty acids on the development of abdominal pain and impaired colonic motility in IBS patients with overweight and obesity. The literature search was conducted in the databases Embase, PubMed and Google Scholar using the keywords “irritable bowel syndrome”, “obesity”, “short-chain fatty acids”, “gut microbiota”.

#205 Features of chronic kidney disease in patients with obesity and arterial hypertension

Abstract Background and Aims to assess the indicators of composite body composition in patients with obesity and chronic kidney disease with arterial hypertension. Method 59 patients with obesity and arterial hypertension were examined. When selecting patients, inclusion criteria were taken into account: men and women aged 25 to 55 years, obesity (BMI more than 30 kg/m²; waist circumference (WC) more than 80 cm in women and more than 94 cm in men), presence of hypertension I– Stage II, grade 1–2, absence of renal pathology (history of kidney disease, structural changes in the parenchyma and vessels of the kidneys during ultrasound examination, changes in urinary sediment and urine density, proteinuria, decreased GFR less than 60 ml/min/1.73 m² ), signed informed consent. Metabolically complicated obesity was defined as the presence of abdominal obesity, a BMI of more than 30 kg/m2 in combination with hypertension and ≥ 2 cardiometabolic abnormalities. A metabolically healthy obesity phenotype was considered to be the presence of obesity without hypertension, dyslipidemia, or hyperglycemia. The results obtained during the study were compared with the indicators of a control group formed from 30 practically healthy individuals aged 25–55 years without obesity or overweight. Differences in age, gender, duration of hypertension and obesity were not established. Metabolic activity of adipose tissue was assessed by the level of leptin, soluble leptin receptors (sLR), adiponectin, resistin, free leptin index (FLI), leptin/adiponectin index (L/A). Renal function: GFR (CKD EPI and Hoek), serum and urine cystatin C, albuminuria. The composite composition of the body was studied using bioimpedance analysis using an ABC-01 Medass analyzer of body composition and balance of water sectors of the body. Results In a comparative analysis of the parameters of the composite body composition in the obese groups, the highest values ​​of fat mass (42.8 ± 6.8 and 35 ± 4.2 kg) and total fluid (40.2 ± 5.0 and 36.0 ± 2.8 kg) with a reduced proportion of 17 active cell mass (ACM) (53.0 ± 3.2 and 56.1 ± 3.4%) were detected in patients with complicated obesity (p &amp;lt; 0.05). Regardless of the obesity phenotype, correlations were established: between the level of diastolic blood pressure (DBP) and the volume of total (r1 = 0.42; r2 = 0.52) and extracellular fluid (r1 = 0.50; r2 = 0.60); level of DBP and urinary excretion of cystatin C (r1 = 0.51; r2 = 0.61) (p &amp;lt; 0.01). A decrease in the proportion of ACM in obese groups was associated with an increase in resistin levels (r1 = −0.56; r2 = −0.31). In obese groups, regardless of phenotype, fat mass was associated with leptin levels (r1 = 0.52; r2 = 0.42) and free leptin index (FLI) (r1 = 0.75; r2 = 0.46 ) (p &amp;lt; 0.05). In group 1, a positive correlation was additionally established for the volume of fat mass with systolic blood pressure (SBP) (r1 = 0.70) and DBP (r1 = 0.65), with the level of uric acid (r1 = 0.57), cholesterol LDL (r1 = 0.52), cystatin C in urine (r1 = 0.75) and insulin resistance index (HOMA-IR) (r1 = 0.65) (p &amp;lt; 0.01). Conclusion Body mass index does not determine the obesity phenotype. In patients with complicated obesity, the proportion of fat mass is higher than in metabolically healthy obesity and is associated with increased levels of glucose and uric acid. All obese patients are characterized by an increase in the percentage of total and extracellular fluid, associated with the level of blood pressure and urinary excretion of markers of tubular dysfunction.

Brown adipose tissue metabolism in women is dependent on ovarian status.

In rodents, loss of estradiol (E2) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (n = 27; 35 ± 9 yr; body mass index = 26.0 ± 5.3 kg/m2) and postmenopausal (n = 25; 51 ± 8 yr; body mass index = 28.0 ± 5.0 kg/m2) women at room temperature and during acute cold exposure using [11C]acetate with positron emission tomography coupled with computed tomograph. BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18F]fluoro-d-glucose. To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (n = 8; 40 ± 4 yr; BMI = 28.0 ± 7.2 kg/m2) after 6 mo of gonadotropin-releasing hormone agonist therapy to suppress ovarian hormones. At room temperature, there was no difference in BAT oxidative metabolism between premenopausal (0.56 ± 0.31 min-1) and postmenopausal women (0.63 ± 0.28 min-1). During cold exposure, BAT oxidative metabolism (1.28 ± 0.85 vs. 0.91 ± 0.63 min-1, P = 0.03) and net BAT glucose uptake (84.4 ± 82.5 vs. 29.7 ± 31.4 nmol·g-1·min-1, P < 0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent gonadotropin-releasing hormone agonist, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36 ± 0.66 min-1 to 0.91 ± 0.41 min-1) to that observed in postmenopausal women (0.91 ± 0.63 min-1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.NEW & NOTEWORTHY In rodents, loss of estrogen reduces brown adipose tissue (BAT) activity. Whether this is true in humans is not known. We found that BAT oxidative metabolism and glucose uptake were lower in postmenopausal compared to premenopausal women. In premenopausal women who underwent ovarian suppression to reduce circulating estrogen, BAT oxidative metabolism was reduced to postmenopausal levels. Thus the loss of ovarian function in women leads to a reduction in BAT metabolic activity independent of age.

A decreased level of high-density lipoprotein is a possible risk factor for type 2 diabetes mellitus: A review.

Type 2 diabetes mellitus (T2DM) is characterized primarily by dyslipidemia and hyperglycemia due to insulin resistance. High-density lipoprotein (HDL) play a significant role in preventing the incidence of dyslipidemia and its complications. HDL has different protective functions, such as reducing oxidation, vascular inflammation, and thrombosis; additionally, its anti-diabetic role is one of the most significant recent discoveries about HDL and some of its constituent lipoproteins. This research reviews ongoing studies and preliminary investigations into the assessment of relation between decreased level of HDL and T2DM. The levels of HDL and its functions contribute to glucose hemostasis and the development of T2DM through four possible mechanisms, including insulin secretion by beta cells, peripheral insulin sensitivity, non-insulin-dependent glucose uptake, and adipose tissue metabolic activity. Additionally, the anti-oxidant properties of HDL protect beta cells from apoptosis caused by oxidative stress and inflammation induced by low-density lipoprotein, which facilitate insulin secretion. Therefore, HDL and its compositions, especially Apo A-I, play an important role in regulating glucose metabolism, and decreased levels of HDL can be considered a risk factor for DM. Different factors, such as hypoalphalipoproteinemia that manifests as a consequence of genetic factors, such as Apo A-I deficiency, as well as secondary causes arising from lifestyle choices and underlying medical conditions that decrease the level of HDL, could be associated with DM. Moreover, intricate connections between HDL and diabetic complications extend beyond glucose metabolism to encompass complications like cardiovascular disease and kidney disease. Therefore, the exact interactions between HDL level and DM should be evaluated in future studies.

MM-125 Adipose Tissue Metabolic Activity in Multiple Myeloma

MM-125 Adipose Tissue Metabolic Activity in Multiple Myeloma

Comprehensive Assessment of Cardiometabolic Risk in Patients with Chronic Obstructive Pulmonary Disease and Obesity

Background: Currently, comorbid patients with chronic obstructive pulmonary disease (COPD) and obesity are becoming increasingly common in clinical practice. The objective of this study was to conduct a comparative analysis of indicators of various types of body metabolism (carbohydrate, lipid, adipokine profile) in COPD patients with obesity and normal body weight. Methods and Results: The study included 86 patients with COPD (GOLD 3-4, group D). The diagnosis of COPD was established in accordance with GOLD, revision 2021.The patients were divided into two groups. Group 1 consisted of 43 COPD patients with NBW [31(72.7%) men and 12(27.3%) women aged 43 to 75 years (mean age of 62.40 ± 8.83 years)] and Group 2 consisted of 43 COPD patients with obesity [32(77.27%) men and 11(22.73%) women aged 48 to 72 years (mean age of 62.94 ± 5.96 years)]. All patients underwent an analysis of the composition of the body by the bioelectrical impedance method. Blood levels of total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C were determined by the enzymatic colorimetric method. The glucose level was determined by the glucose oxidant method. The serum adipokine levels (leptin, adiponectin, resistin), as well as testosterone and immunoreactive insulin, were determined using ELISA. To assess insulin resistance, the HOMA-IR index was calculated. To determine cardiovascular risk, the visceral adiposity index (VAI) was calculated according to the formula, which considers body mass index, triglycerides, HDL-C, and waist circumference. The level of HDL-C was significantly lower (P=0.0000)), and the levels of TC (P=0.0479), LDL-C (P=0.0020), glucose (P=0.0020), immunoreactive insulin (P=0.0000), and HOMA-IR index (P=0.0000), were significantly higher in Group 2 than in Group 1. As for the content of adipose tissue hormones, the leptin level was significantly higher in Group 2 (P=0.0000) than in Group 1, while there were no statistically significant differences between groups in the level of resistin (P=0.4996). The adiponectin level was significantly lower in Group 2 than in Group 1 (P&lt;0.0001). The VAI level in Group 2 was significantly higher than in Group 1 (2.13±1.56 and 1.18±0.41, respectively, P=0.0002). In contrast, the testosterone level was significantly lower in Group 2 than in Group 1 (10.59±6.94 nmol/l and 20.02±12.25 nmol/l, respectively, P=0.0000). Conclusion: The high metabolic activity of adipose tissue in patients with COPD and obesity is directly related to the progression of comorbid conditions.

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.

¿Es la actividad metabólica del tejido adiposo un predictor de respuesta histopatológica al tratamiento neoadyuvante en el cáncer de mama?

Introduction and objectivePrediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is essential for optimal treatment strategy. The current approach of adjuvant or neoadjuvant treatment is based on the molecular subtype. Obesity may have affected chemotherapy response. This study aims to evaluate the relationship between metabolic activity of adipose tissue (AT) and pathological responses to NAC. And to define the association with body mass index (BMI) and metabolic parameters of standardized uptake value (SUV) of adipose tissue measured by positron emission computed tomography (PET/CT). Material and methodsOne-hundred and sixteen consecutive patients with stage II and III breast cancer who underwent PET/CT before receiving NAC, were evaluated in the study. Metabolic parameters of visceral adipose tissue (VAT-SUV), subcutaneous adipose tissue (SAT-SUV), and calculated SUV of visceral-to-subcutaneous ratio (V/S-ratio) were regarded. The relationship between SUV of AT and pathologic response was evaluated from medical records retrospectively. ResultsUnivariate-analysis revealed that good pathological response was significantly associated with clinical stage (p<0.001), HER-2 positivity (p<0.001), VAT-SUV (p=0.037), VAT-density (p=0.043) and V/S-ratio (p=0.003). In multivariate-analysis clinical stage, HER-2 positivity and V/S-ratio were found to have statistically effect on pathological response. VAT-volume (p<0.001), VAT-SUV (p=0.016), SAT-volume (p<0.001) and SAT-SUV (p<0.001) has positive correlation with BMI value. On the other hand, V/S-ratio (p=0.039) and SAT-density (p=0.003) has negative correlation with BMI. ConclusionMetabolic activity of AT is associated with BMI and effected chemotherapy responses. Low V/S ratio was associated with high BMI and poor pathological response to NAC. V/S ratio may be a useful marker for the prediction of NAC responses.

Impact of Testosterone Deficiency on Adipose Tissue Metabolic Activity and Plasma Lipoprotein and Glucose Homeostasis: The Role of Apolipoprotein E2 and E4 Isoforms

Background: Recent findings indicate that testosterone deficiency (TD) affects key metabolic processes, such as lipid and carbohydrate metabolism. Apolipoprotein E (APOE) is the natural ligand for the low-density lipoprotein receptor (LDLR). The natural APOE isoforms APOE3 and APOE4 have a high affinity for LDLR, while APOE2 exhibits impaired binding to the receptor and an inability to promote lipoprotein remnant clearance. Previous work indicated that LDLR modulates the effects of TD on adipose tissue mitochondrial metabolic activity. Here, we investigated how APOE2 or APOE4 expression influences the effects of TD on plasma lipid and glucose homeostasis and white adipose tissue and brown adipose tissue (BAT) mitochondrial metabolic activity. Materials and Methods: APOE2 knock-in (Apoe2knock-in) and APOE4 knock-in (Apoe4knock-in) mice were subjected to surgical castration or sham operation. Mice were fed western-type diet for a period of 12 weeks, and a series of analyses were performed on live animals or specimens collected at the end of the study. Results: TD results in body weight loss only in Apoe4knock-in mice. Castrated Apoe2knock-in mice show much reduced BAT mitochondrial uncoupling protein 1 (Ucp1) and CytC expression, which may explain the body weight difference between castrated Apoe2knock-in and Apoe4knock-in mice. The reduced body weight gain in castrated APOE4-expressing mice did not alleviate the already much impaired glucose tolerance of these mice or their hepatic triglyceride levels. Quite strikingly, in both mouse strains hypogonadism brings about negative effects on lipoprotein metabolism, manifested by different disturbances. Conclusions: TD is associated with distinct metabolic abnormalities, which depend on the APOE isoform expressed.

Is adipose tissue metabolic activity a predictor of pathological responses to neoadjuvant treatment in breast cancer

Introduction and objectivePrediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is essential for optimal treatment strategy. The current approach of adjuvant or neoadjuvant treatment is based on the molecular subtype. Obesity may have affected chemotherapy response. This study aims to evaluate the relationship between metabolic activity of adipose tissue (AT) and pathological responses to NAC. And to define the association with body mass index (BMI) and metabolic parameters of standardized uptake value (SUV) of adipose tissue measured by positron emission computed tomography (PET/CT). Material and methodsOne-hundred and sixteen consecutive patients with stage II and III breast cancer who underwent PET/CT before receiving NAC, were evaluated in the study. Metabolic parameters of visceral adipose tissue (VAT-SUV), subcutaneous adipose tissue (SAT-SUV), and calculated SUV of visceral-to-subcutaneous ratio (V/S-ratio) were regarded. The relationship between SUV of AT and pathologic response was evaluated from medical records retrospectively. ResultsUnivariate-analysis revealed that good pathological response was significantly associated with clinical stage (P<.001), HER-2 positivity (P<.001), VAT-SUV (P=.037), VAT-density (P=.043) and V/S-ratio (P=.003). In multivariate-analysis clinical stage, HER-2 positivity and V/S-ratio were found to have statistically effect on pathological response. VAT-volume (P<.001), VAT-SUV (P=.016), SAT-volume (P<.001) and SAT-SUV (P<.001) has positive correlation with BMI value. On the other hand, V/S-ratio (P=.039) and SAT-density (P=.003) has negative correlation with BMI. ConclusionMetabolic activity of AT is associated with BMI and effected chemotherapy responses. LowV/S ratio was associated with high BMI and poor pathological response to NAC. V/S ratio may be a useful marker for the prediction of NAC responses.

Mitochondrial transformation occurs in cultured adipocytes, but fails to increase adipose tissue metabolic activity in mice in vivo

ABSTRACT A large number of studies in recent years have aimed to devise novel therapeutic strategies to increase adipose tissue metabolic activity and fight the global obesity epidemics. Growing evidence suggests that cells are able to accept isolated mitochondria by a simple coincubation in a process known as mitochondrial transformation. Therefore, we aimed to test whether mitochondrial transformation occurs in mature adipocytes, and whether this phenomenon could be utilized as a therapeutic approach to increase adipose tissue mitochondrial content and improve metabolic control. We provide evidence that both brown and white adipocytes are able to rapidly accept a large amount of brown adipocyte-derived mitochondria, which remain functional for several days and significantly contribute to cellular respiration in vitro. However, we did not find any evidence that internalization of exogenous mitochondria would trigger transcriptional changes in the recipient cells. Moreover, injection of a large amount of brown adipocyte-derived mitochondria into the inguinal fat of C57BL/6 mice failed to increase whole-body energy expenditure, and reduce body weight gain under obesogenic conditions. This might be due to activation of immune response and rapid removal of administered mitochondria. Altogether, our study adds information on the usability of mitochondrial transformation in the treatment of metabolic disease.

Benefits of a fixed-dose combination of standardized P. mume extract with choline on adipose tissue mitochondrial metabolic activity and pancreatic β-islet secretory capacity in mice

BackgroundA fixed dose combination (FDC) of P.mume standardized extract with choline, was shown to provide significant benefit to the early stages of non-alcoholic fatty liver disease (NAFLD). PurposeGiven the close association of NAFLD with obesity and type 2 diabetes mellitus, in this study we investigated how this FDC may also benefit adipose tissue metabolic activity and pancreatic β-islet insulin secretion. Study designGroups of C57BL/6 mice fed high-fat diet were treated with FDC or left untreated for a period of 15 or 24 weeks. MethodsPlasma and adipose tissue samples were isolated and biochemical and molecular analyses were performed. Mitochondrial uncoupling protein 1 (Ucp1) and Cytochrome C (CytC)protein levels were used as biomarkers of non-shivering thermogenesis and oxidative phosphorylation respectively. Pancreatic β-islet secretory capacity was assessed by glucose stimulated insulin secretion assay. ResultsOur data indicate that treatment of mice with this FDC resulted in significant and persistent weight loss due to increased brown adipose tissue mitochondrial non-shivering thermogenesis through Ucp1. Moreover, treated mice presented improved glucose tolerance compared to their untreated counterparts, due to improved pancreatic β-islet secretory capacity. A significant benefit on hepatic lipid deposition and NAFLD development was also noted, consistent with the findings from previous clinical trials. ConclusionsOur findings support that in addition to the early stages of NAFLD, this FDC provides significant pharmacological benefit on weight loss and plasma glucose homeostasis. These finding may have significant implications on the prediabetic state where nutritional and lifestyle changes is the only recommended strategy.

1314-P: Activating GABAergic Neurons in the Caudal Preoptic Area Promote Energy Expenditure in Diet-Induced Obesity

Obesity results from the imbalance between energy intake and energy expenditure, which are tightly regulated by dynamic hypothalamic circuits. Our goal is to identify and leverage hypothalamic components that promote energy expenditure for successful weight loss. Vesicular communication by ventromedial hypothalamic nucleus (VMN) steroidogenic factor 1 (Sf1) neurons is required for maintaining body weight, due at least in part to stimulating metabolic activity in adipose tissue, but the mechanistic details are unclear. VMNSf1 neurons efferently communicate with relatively few places in the brain but the most prominent projections are in the most caudal regions of the preoptic area (cPOA) (+0.1 to -0.3mm bregma, lateral to the suprachiasmatic nucleus) . We tested the hypothesis that GABAergic cPOA neurons promote energy expenditure and weight loss by activating either GABAergic or glutamatergic neurons via hM3dq, using vGATCre (vesicular GABAergic transporter) or vGLUT2Cre (vesicular glutamatergic transporter 2) in diet-induced obese male mice. Activating vGATcPOA neurons reduced body weight and adiposity without altering food intake. Activating vGLUT2cPOA neurons reduced body weight and food intake but did not reduce adiposity. Activating vGLUT2cPOA neurons reduced core body temperature, but not vGATcPOA neurons. We are currently investigating the mechanisms for how vGATcPOA neurons reduce adiposity. Weight loss is not likely mediated by direct inhibition of vGLUT2cPOA neurons because diet induced obese male mice with CNO-initiated signaling of hM4di in vglut2cPOA neurons does not reduce adiposity or body weight. Alternatively, vGATcPOA neurons may communicate with a distinct efferent system. Indeed, vGATcPOA, but not vGLUT2cPOA, neurons project to the lateral hypothalamus and medial raphe. Future studies will reveal the functional connection between VMNSf1 neurons and vGATcPOA neurons, and the descending circuitry that promotes energy expenditure. Disclosure R.Basu: None. A.J.Elmendorf: Research Support; Eli Lilly and Company. C.A.Mahler: Stock/Shareholder; AstraZeneca, Pfizer Inc. J.Flak: Research Support; Eli Lilly and Company. Funding American Diabetes Association (17-INI-15) ; IU CDMD NIH/NIDDK (P30 DK097512)

Prognostic Significance of Adipose Tissue Distribution and Metabolic Activity in PET/CT in Patients with Metastatic Colorectal Cancer.

In this study, we aimed to evaluate the prognostic significance of adipose tissue distribution and metabolic activity in PET/CT to predict survival in patients with metastatic colorectal cancer (mCRC). The volume, density (HU), and FDG uptake (standardized uptake value (SUV)) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and maximum FDG uptake of the tumor tissue were measured. Subcutaneous adipose tissue of volume-to-density ratio (SAT ratio) was calculated. The median OS for the patients with SAT ratio value < -1.1 and ≥ -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). During follow-up, 69 patients experienced disease progression. The median progression-free survival (PFS) was 11.03months (95% CI: 9.11-12.95). Median PFS for patients with tumor SUV max value < 11.5 and ≥ 11.5 were 9.2 (95% CI 7.25-11.27) and 12.6 (95% CI 10.02-15.27) months, respectively (p = 0.14). Forty-eight patients received bevacizumab therapy. VAT SUV mean (HR: 0.09; 95% CI 0.01-0.52, p = 0.008) was significantly associated with PFS in patients receiving bevacizumab. SAT ratio was the significant parameter for the OS (HR: 0.58; 95% CI 0.33-1.01, p = 0.05) and PFS (HR: 1.99; 95% CI 1.02-3.91, p = 0.043). SAT ratio was an independent prognostic factor for survival in patients with mCRC. Higher SAT volume is correlated with longer survival in mCRC patients.

The Effects of Exercise on White and Brown Adipose Tissue Cellularity, Metabolic Activity and Remodeling.

Emerging evidence suggests a significant functional role of adipose tissue in maintaining whole-body metabolic health. It is well established that obesity leads to compositional and morphological changes in adipose tissue that can contribute to the development of cardiometabolic disorders. Thus, the function and size of adipocytes as well as perfusion and inflammation can significantly impact health outcomes independent of body mass index. Lifestyle interventions such as exercise can improve metabolic homeostasis and reduce the risk for developing cardiometabolic disorders. Adipose tissue displays remarkable plasticity in response to external stimuli such as dietary intervention and exercise. Here we review systemic and local effects of exercise that modulate white and brown adipose tissue cellularity, metabolic function and remodeling in humans and animals.

Measuring Visceral Adipose Tissue Metabolic Activity in Sleep Apnea Utilizing Hybrid 18F-FDG PET/MRI: A Pilot Study.

PurposeVisceral adipose tissue (VAT) is proinflammatory and is associated with cardiovascular (CV) disease. We investigated the relationship between obstructive sleep apnea (OSA) and visceral adipose tissue (VAT) metabolic activity in a pilot group of patients using positron-emission tomography/magnetic resonance imaging (PET/MRI) with 18F-fluorodeoxyglucose (FDG) tracer as a novel marker of adipose tissue inflammation.Patients and MethodsWe analyzed patients from an ongoing study, recruiting those with newly diagnosed, untreated OSA (Respiratory Disturbance Index [RDI] ≥ 5), using home sleep apnea testing (WatchPAT-200 Central-Plus). PET/MRI scans were acquired before continuous positive airway pressure (CPAP)-initiation, and after 3 months of CPAP therapy. Adipose tissue metabolic activity (18F-FDG-uptake) was measured using standardized uptake values (SUV) within the adipose tissue depots. The primary outcome was VAT SUVmean, and secondary outcomes included VAT volume, and subcutaneous adipose tissue (SAT) volume/SUVmean. Reproducibility and reliability of outcome measures were analyzed using intraclass correlation coefficients (ICC). Multivariable linear regression was used to evaluate the association between OSA and primary/secondary outcomes.ResultsOur analytical sample (n = 16) was 81% male (mean age 47 ± 15 years, mean BMI of 29.9 ± 4.8kg/m2). About 56% had moderate to severe OSA (mean RDI 23 ± 6 events/hour), and 50% were adherent to CPAP. We demonstrated excellent inter/intra-rater reliability and reproducibility for the primary and secondary outcomes. Patients with moderate-to-severe OSA had a higher VAT SUV mean compared to those with mild OSA (0.795 ± 0.154 vs 0.602 ± 0.19, p = 0.04). OSA severity was positively associated with VAT SUVmean (primary outcome), adjusted for age and BMI (B [SE] = 0.013 ± 0.005, p = 0.03). Change in VAT volume was inversely correlated with CPAP adherence in unadjusted analysis (B [SE] = −48.4 ± 18.7, p = 0.02).ConclusionDerangements in VAT metabolic activity are implicated in adverse cardiometabolic outcomes and may be one of the key drivers of CV risk in OSA. Our results are hypothesis-generating, and suggest that VAT should be investigated in future studies using multi-modal imaging to understand its role as a potential mediator of adverse cardiometabolic risk in OSA.

The role of resistin and its relation to other pathogenetic factors of the chronic kidney disease development

Chronic kidney disease (CKD) is the leading cause of death from non-communicable diseases, and its prevalence in 2017 ranged from 8.5 to 9.8%. Depending on the stage of CKD, stage 1 was diagnosed in 3.5%, stage 2 in 3.2% and stage 3 in 7.6%, while stages 4 and 5 took place in 0.4 and 0.1% of the world’s population respectively. Obesity also contributes to the increase in the prevalence and severity of CKD, and their combination occurs in 3.1% of patients. Kidney damage and their structural and functional changes in patients with obesity are associated with high metabolic activity of adipose tissue, due to the synthesis of adipocytokines, including resistin.The purpose of the work: to study changes of resistin level in the blood in patients with early stages of chronic kidney disease, its relation to the level of endothelin, markers of lipid metabolism and inflammation.Materials and methods: 70 patients with stage 1 and 88 patients with stage 2 of CKD with different stages of obesity were examined. Glomerular filtration rate (GFR) was calculated by the formula CKD-EPI based on creatinine, cystatin C and their combination (CKD-EPIcysC / cr). The levels of cystatin C, resistin, tumor necrosis factor-alpha (TNF-α) and endothelin-1 were determined by enzyme-linked immunosorbent assay. Determination of total cholesterol and low-density lipoprotein cholesterol levels in the blood serum was performed by colorimetric method. Statistical analysis of the results was performed with the help of Statistica 6.0 statistical software package using Student’s t-test and Spearman’s rank correlation coefficient.Results: an increase of the resistin level in the blood by 1.3 times in the patients with stage 1 CKD and by 1.6 times in the patients with stage 2 CKD and obesity was determined (p1.2 &amp;lt; 0.05), and there was a weak correlation between its concentration in the blood and body mass index. A significant average negative correlation between resistin and GFR was detected. Increased serum resistin level correlates with increased TNF-α. In patients of both groups, the level of resistin and LDL increases simultaneously, and the correlation between them increases as CKD progresses. Similar changes are observed with respect to increasing concentrations of resistin and endothelin-1. Thus, an increase of resistin level in the blood in patients with the early stages of CKD initiates a number of pathological changes, such as systemic inflammation, hyperlipidemia and endothelial dysfunction.