Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Citrulline And Adi-Peg20 Reduce Inflammation In A Juvenile Porcine Model Of Acute Endotoxemia, Caitlin Vonderohe, Barbara Stoll, Inka Didelija, Trung Nguyen, Mahmoud Mohammad, Yava Jones-Hall, Miguel A Cruz, Juan Marini, Douglas Burrin

Faculty, Staff and Students Publications

BACKGROUND: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of …

Diet-Stimulated Marrow Adiposity Fails To Worsen Early, Age-Related Bone Loss, Cody Mcgrath, Sarah E Little-Letsinger, Gabriel M Pagnotti, Buer Sen, Zhihui Xie, Gunes Uzer, Guniz B Uzer, Xiaopeng Zong, Martin A Styner, Janet Rubin, Maya Styner

Faculty, Staff and Student Publications

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood.

Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed …

Cardiovascular Risk Factors In Sheehan's Syndrome: A Case-Control Study, Mayur Agrawal, Subhash C Yadav, Swish K Singh, Sheo Kumar, Krishnarpan Chatterjee, Naveen K Garg

Faculty, Staff and Student Publications

INTRODUCTION: Obesity, dyslipidaemia and insulin resistance are associated with hypopituitarism. The association between these conditions and Sheehan's syndrome (SS) caused by post-partum pituitary gland necrosis is poorly understood. This study aimed to assess cardiovascular risk surrogate markers in SS patients, and we compared clinical, biochemical and radiological testing with healthy controls.

METHODS: In this cross-sectional study, we studied 45 patients with SS on standard replacement therapy and compared them with healthy controls. All subjects underwent anthropometric, inflammatory marker and hormonal measurement (adrenocorticotropic hormone (ACTH), stimulated cortisol, insulin-like growth factor-1 (IGF-1), thyroxine (T4), follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), …

Gut Microbiome And Hepatic Transcriptomic Determinants Of Hcc Development In Mice With Metabolic Dysfunction-Associated Steatohepatitis, Lillian I Dolapchiev, Kristyn A Gonzales, Lorenzo R Cruz, Mihai Gagea, Heather L Stevenson, Suet-Ying Kwan, Laura Beretta

Faculty, Staff and Student Publications

Purpose: Hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) is often diagnosed at a late stage, and its incidence is increasing. Predictive biomarkers are therefore needed to identify individuals at high risk of HCC. We aimed to characterize the gut microbiome and hepatic transcriptome associated with HCC development in female mice with hepatocyte-deletion of Pten (HepPten -). These mice present with large variations in HCC development, making them a powerful model for biomarker discovery.

Methods & results: Sequencing of stool 16S and hepatic RNA was performed on a first set of mice. Among all liver histology …

Variant Of The Lactase Lct Gene Explains Association Between Milk Intake And Incident Type 2 Diabetes, Kai Luo, Guo-Chong Chen, Yanbo Zhang, Jee-Young Moon, Jiaqian Xing, Brandilyn A Peters, Mykhaylo Usyk, Zheng Wang, Gang Hu, Jun Li, Elizabeth Selvin, Casey M Rebholz, Tao Wang, Carmen R Isasi, Bing Yu, Rob Knight, Eric Boerwinkle, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for …