Try a new search

Format these results:

Searched for:



Total Results:


The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice

Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A.E.; Park, Christopher Y.; Schlamp, Florencia; Heffron, Sean P.; Fisher, Edward A.; Brathwaite, Collin; Ragolia, Louis
Purpose: Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. Methods: A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8 weeks. Results: After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. Conclusion: Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk. Graphical Abstract: [Figure not available: see fulltext.].
ISSN: 0960-8923
CID: 5630102

Correction: The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice (Obesity Surgery, (2024), 10.1007/s11695-023-07052-w)

Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A.E.; Park, Christopher Y.; Schlamp, Florencia; Heffron, Sean P.; Fisher, Edward A.; Brathwaite, Collin; Ragolia, Louis
The original article has been corrected to replace the Electronic Supplemental Material.
ISSN: 0960-8923
CID: 5629732

Microsomal triglyceride transfer protein regulates intracellular lipolysis in adipocytes independent of its lipid transfer activity

Rajan, Sujith; Hofer, Peter; Christiano, Amanda; Stevenson, Matthew; Ragolia, Louis; Villa-Cuesta, Eugenia; Fried, Susan K; Lau, Raymond; Braithwaite, Collin; Zechner, Rudolf; Schwartz, Gary J; Hussain, M Mahmood
BACKGROUND:The triglyceride (TG) transfer activity of microsomal triglyceride transfer protein (MTP) is essential for lipoprotein assembly in the liver and intestine; however, its function in adipose tissue, which does not assemble lipoproteins, is unknown. Here we have elucidated the function of MTP in adipocytes. APPROACH AND RESULTS/RESULTS:mice maintained higher body temperature by mobilizing more fatty acids. Biochemical studies indicated that MTP deficiency de-repressed adipose triglyceride lipase (ATGL) activity and increased TG lipolysis. Both wild type MTP and mutant MTP deficient in TG transfer activity interacted with and inhibited ATGL activity. Thus, the TG transfer activity of MTP is not required for ATGL inhibition. C-terminally truncated ATGL that retains its lipase activity interacted less efficiently than full-length ATGL. CONCLUSION/CONCLUSIONS:Our findings demonstrate that adipose-specific MTP deficiency increases ATGL-mediated TG lipolysis and enhances energy expenditure, thereby resisting diet-induced obesity. We speculate that the regulatory function of MTP involving protein-protein interactions might have evolved before the acquisition of TG transfer activity in vertebrates. Adipose-specific inhibition of MTP-ATGL interactions may ameliorate obesity while avoiding the adverse effects associated with inhibition of the lipid transfer activity of MTP.
PMID: 36228741
ISSN: 1532-8600
CID: 5352142

Underestimation of SARS-CoV-2 infection in placental samples [Letter]

Hanna, Nazeeh; Lin, Xinhua; Thomas, Kristen; Vintzileos, Anthony; Chavez, Martin; Palaia, Thomas; Ragolia, Louis; Verma, Sourabh; Khullar, Poonam; Hanna, Iman
PMID: 34297970
ISSN: 1097-6868
CID: 4954872

Lipocalin-type Prostaglandin D2 Synthase appears to function as a Novel Adipokine Preventing Adipose Dysfunction in response to a High Fat Diet

Srivastava, Ankita; Palaia, Thomas; Hall, Christopher; Stevenson, Matthew; Lee, Jenny; Ragolia, Louis
Adipose dysfunction is the primary defect in obesity that contributes to the development of dyslipidemia, insulin resistance, cardiovascular diseases, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and some cancers. Previously, we demonstrated the development of NAFLD in lipocalin-type prostaglandin D2 synthase (L-PGDS) knockout mice regardless of diet. In the present study, we examined the role of L-PGDS in adipose in response to a high fat diet. We observed decreased expression of L-PGDS in adipose tissue and concomitant lower plasma levels in a dietary model of obesity as well as in insulin resistant 3T3-L1 adipocytes. We show reduced adiponectin expression and phosphorylation of AMPK in white adipose tissue of L-PGDS KO mice after 14 weeks on a high fat diet as compared to control C57BL/6 mice. We also observe an increased fat content in L-PGDS KO mice as demonstrated by adipocyte hypertrophy and increased expression of lipogenenic genes. We confirmed our in vivo findings in in vitro 3T3-L1 adipocytes, using an enzymatic inhibitor of L-PGDS (AT56). Rosiglitazone treatment drastically increased L-PGDS expression in insulin resistant 3T3-L1 adipocytes and increased adiponectin expression and AMPK phosphorylation in AT56 treated 3T3-L1 adipocytes. We conclude that the absence of L-PGDS has a deleterious effect on adipose tissue functioning, which further reduces insulin sensitivity in adipose tissue. Consequently, we propose L-PGDS appears to function as a potential member of the adipokine secretome involved in the regulation of the obesity-associated metabolic syndrome.
PMID: 34371198
ISSN: 1098-8823
CID: 5032532

RYGB Is More Effective than VSG at Protecting Mice from Prolonged High-Fat Diet Exposure: An Occasion to Roll Up Our Sleeves?

Stevenson, Matthew; Srivastava, Ankita; Lee, Jenny; Hall, Christopher; Palaia, Thomas; Lau, Raymond; Brathwaite, Collin; Ragolia, Louis
PURPOSE/OBJECTIVE:Understanding the effects of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on adipose tissue physiology is important for the treatment of obesity-related metabolic disorders. By using robust mouse models of bariatric surgery that closely resemble those performed in humans, we can compare the effects of RYGB and VSG on adipose physiology in the absence of post-operative confounds such as diet and lifestyle changes. MATERIALS AND METHODS/METHODS:RYGB and VSG were compared using a diet-induced mouse model of obesity. High-fat diet (HFD) was administered post-operatively and changes to white and brown adipose tissue were evaluated, along with alterations to weight, glucose homeostasis, dyslipidemia, and insulin sensitivity. RESULTS:After prolonged exposure to high-fat diet post-operatively, RYGB was effective in achieving sustained weight loss, while VSG unexpectedly accelerated weight gain rates. The resolution of obesity-related comorbidities such as glucose and insulin intolerance, dyslipidemia, and insulin sensitivity was improved after RYGB, but not for VSG. In RYGB, there were improvements to the function and health of white adipose tissue, enhanced brown adipose metabolism, and the browning of subcutaneous white adipose tissue, with no comparable changes seen for these factors after VSG. Some markers of systemic inflammation improved after both RYGB and VSG. CONCLUSION/CONCLUSIONS:There are significantly different effects between RYGB and VSG when HFD is administered post-operatively and robust mouse models of bariatric surgery are used. RYGB resulted in lasting physiological and metabolic changes but VSG showed little difference from that of its sham-operated, DIO counterpart.
PMID: 33856636
ISSN: 1708-0428
CID: 4889082

COVID-19 Infection and Placental Histopathology in Women Delivering at Term

Patberg, Elizabeth T; Adams, Tracy; Rekawek, Patricia; Vahanian, Sevan A; Akerman, Meredith; Hernandez, Andrea; Rapkiewicz, Amy V; Ragolia, Louis; Sicuranza, Genevieve; Chavez, Martin R; Vintzileos, Anthony M; Khullar, Poonam
BACKGROUND:- There is a paucity of data describing the effects of COVID-19, especially in asymptomatic patients, on placental pathology. Although the pathophysiology of COVID-19 is not completely understood, there is emerging evidence that it causes a severe systemic inflammatory response and results in a hypercoagulable state with widespread microthrombi. We hypothesized that it is plausible that a similar disease process may occur in the fetal-maternal unit. OBJECTIVE:- The aim of this study was to determine whether COVID-19 in term patients admitted to Labor and Delivery, including women without COVID-19 symptomatology, is associated with increased placental injury compared to a cohort of COVID-19 negative controls. STUDY DESIGN/METHODS:- This was a retrospective cohort study performed at NYU Winthrop Hospital between 3/31/2020 and 6/17/2020. During the study period all women admitted to Labor and Delivery were routinely tested for SARS-CoV-2 regardless of symptomatology. The placental histopathological findings of COVID-19 patients (n=77) who delivered a singleton gestation at term were compared to a control group of term patients without COVID-19 (n=56). Controls were excluded if they had obstetric or medical complications including fetal growth restriction, oligohydramnios, hypertension, diabetes, coagulopathy or thrombophilia. Multivariable logistic regression models were performed for variables that were significant in univariable analyses. A subgroup analysis was also performed comparing asymptomatic COVID-19 cases to negative controls. RESULTS:- In univariable analyses, COVID-19 cases were more likely to have evidence of fetal vascular malperfusion, i.e. presence of avascular villi and/or mural fibrin deposition (32.5% (25/77) vs. 3.6% (2/56), p<0.0001) and villitis of unknown etiology (20.8% (16/77) vs. 7.1% (4/56), p=0.030). These findings persisted in a subgroup analysis of asymptomatic COVID-19 cases compared to COVID-19 negative controls. In a multivariable model adjusting for maternal age, race/ethnicity, mode of delivery, preeclampsia, fetal growth restriction and oligohydramnios, the frequency of fetal vascular malperfusion abnormalities remained significantly higher in the COVID-19 group (OR= 12.63, 95% CI [2.40, 66.40]). While the frequency of villitis of unknown etiology was more than double in COVID-19 cases compared to controls, this did not reach statistical significance in a similar multivariable model (OR=2.11, 95% CI [0.50, 8.97]). All neonates of mothers with COVID-19 tested negative for SARS-CoV-2 by PCR. CONCLUSIONS:- Despite the fact that all neonates born to mothers with COVID-19 were negative for SARS-CoV-2 by PCR, we found that COVID-19 in term patients admitted to Labor and Delivery is associated with increased rates of placental histopathologic abnormalities, particularly fetal vascular malperfusion and villitis of unknown etiology. These findings appear to occur even among asymptomatic term patients.
PMID: 33091406
ISSN: 1097-6868
CID: 4642442

Effect of vitamin D on bone strength in older African Americans: a randomized controlled trial

Dhaliwal, R; Islam, S; Mikhail, M; Ragolia, L; Aloia, J F
There is controversy over whether African Americans have higher vitamin D requirements than recommended by the Institute of Medicine. We previously reported that maintaining serum 25(OH)D above 30 ng/mL does not prevent age-related bone loss. Herein, we report that bone strength is also unaffected by maintaining this level in this population.
PMID: 31938818
ISSN: 1433-2965
CID: 4955002

Lipocalin-type prostaglandin D2 synthase deletion induces dyslipidemia and non-alcoholic fatty liver disease

Kumar, Sunil; Srivastava, Ankita; Palaia, Thomas; Hall, Christopher; Lee, Jenny; Stevenson, Matthew; Zhao, Chaohui Lisa; Ragolia, Louis
Non-alcoholic fatty liver disease (NAFLD) is an emerging risk factor for type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality. Previously, we demonstrated that lipocalin-type prostaglandin D2 synthase (L-PGDS) knockout mice show increased glucose intolerance and accelerated atherosclerosis. In the present study, we investigated the role of L-PGDS in mediating NAFLD utilizing L-PGDS knockout (KO) and control C57BL/6 mice fed either low fat (LFD) or high fat diet (HFD) for 14 weeks. Our present study demonstrates that L-PGDS KO mice remain slightly lighter in weight compared to control mice, yet develop NAFLD faster and eventually progress to the more severe non-alcoholic steatohepatitis (NASH). We found increased lipid accumulation in the liver of KO mice over time on both diets, as compared to control mice. The L-PGDS KO mice showed elevated fasting glucose and insulin levels and developed insulin resistance on both LFD and HFD. Lipogenesis marker proteins such as SREBP-1c and LXRα were increased in L-PGDS KO mice after 14 weeks on both diets, when compared to control mice. We replicated our in vivo findings in vitro using HepG2 cells treated with a combination of free fatty acids (oleic and palmitic acid) and exposure to a L-PGDS inhibitor and prostaglandin D2 receptor (DP1) antagonists. We conclude that the absence or inhibition of L-PGDS results in dyslipidemia, altered expression of lipogenesis genes and the acceleration of NAFLD to NASH, independent of diet and obesity. We propose L-PGDS KO mice as a useful model to explore the pathogenesis of NAFLD and NASH, and L-PGDS as a potential therapeutic target for treatment.
PMID: 32145387
ISSN: 1098-8823
CID: 4371042

Loss of Endothelial FTO Antagonizes Obesity-Induced Metabolic and Vascular Dysfunction

Krüger, Nenja; Biwer, Lauren A; Good, Miranda E; Ruddiman, Claire A; Wolpe, Abigail G; DeLalio, Leon J; Murphy, Sara; Macal, Edgar H; Ragolia, Louis; Serbulea, Vlad; Best, Angela K; Leitinger, Norbert; Harris, Thurl E; Sonkusare, Swapnil K; Gödecke, Axel; Isakson, Brant E
RATIONALE:Increasing prevalence of obesity and its associated risk with cardiovascular diseases demands a better understanding of the contribution of different cell types within this complex disease for developing new treatment options. Previous studies could prove a fundamental role of FTO (fat mass and obesity-associated protein) within obesity; however, its functional role within different cell types is less understood. OBJECTIVES:We identify endothelial FTO as a previously unknown central regulator of both obesity-induced metabolic and vascular alterations. METHODS AND RESULTS:application. CONCLUSIONS:These data identify endothelial FTO as a previously unknown regulator in the development of obesity-induced metabolic and vascular changes, which is independent of its known function in regulation of obesity.
PMID: 31801409
ISSN: 1524-4571
CID: 4954862