About

Professor Dave Bridges is an Associate Professor in the Department of Nutritional Sciences at the University of Michigan, a position he has held since September 1, 2022. The information provided does not include specific details about his research focus, background, or key contributions.

Research topics

• Internal medicine
• Medicine
• Biology
• Endocrinology
• Microbiology
• Chemistry
• Gastroenterology
• Biochemistry
• Genetics
• Immunology

Selected publications

• Lactational Western‐Style Fat Exposure in Mice Programs Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) in Male Offspring

  Molecular Nutrition & Food Research · 2026-04-01

  articleOpen access

  Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of liver disease. Early-life exposure to maternal overnutrition during critical developmental windows, such as lactation, can predispose offspring to develop metabolic disease. We previously demonstrated that consumption of a high fat diet (60% fat) during lactation leads to the development of insulin resistance and MASLD in male offspring. However, no studies have investigated the role of a lactational Western-style fat (45% fat) exposure, which is more clinically relevant and representative of human food consumption habits. Dams were fed either a standard chow or Western-style fat diet from delivery through the 21-day lactation period. At weaning, all offspring were fed standard chow until 3 months of age, when a subset from each group was challenged with an additional high-fat stressor. Exposure to a Western-style fat diet during lactation increased male offspring susceptibility to weight gain, obesity, and insulin resistance when fed a high fat diet in adulthood. Furthermore, these offspring demonstrated hepatomegaly and hepatic triglyceride accumulation, which may be mediated by altered lipid metabolism. These findings indicate that an indirect neonatal exposure to a Western-style fat diet can program male offspring to develop MASLD later in life.

  PublisherDOI

• Association of the Q223R Leptin Receptor Polymorphism With Bacterial Pneumonia in the Michigan Genomics Initiative

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract Background: Bacterial pneumonia is a leading cause of morbidity and mortality and genetic variation may account for differential immune responses in susceptibility and severity of illness. A single nucleotide polymorphism (SNP) in the leptin receptor Q223R (LepR), rs1137101, is associated with a greater susceptibility and severity of illness from E. histolytica and C. difficile in patients and mice with this SNP. Any association between rs1137101 and the occurrence of bacterial pneumonia is unknown. Objective: To investigate the relationship between rs1137101 and the diagnosis of bacterial pneumonia in the Michigan Genomic Initiative (MGI), a resource that combines patient electronic health records and genetic data. Methods: We used data from Freeze 6 of the MGI which included ICD9 or ICD10 codes from 80,381 patients who had been genotyped. The sample population consists of patients with European (86.5%), African (6.2%), Asian (7.4), and Native American (0.9%) ancestry. 54% of the population was female with a mean age of 57.4 ± 6.8 yrs. ICD codes for different types of bacterial pneumonia were mapped to a single phecode phenotype for bacterial pneumonia. However, there were enough patients in MGI with pneumococcal pneumonia to produce a separate phecode category. There were 2098 cases with bacterial pneumonia and 951 with pneumococcal pneumonia and 64,891 controls. Results: There were significant associations between the rs1137101 SNP and bacterial pneumonia (OR=1.1, P=0.003) and pneumococcal pneumonia (OR 1.15, P=0.004) diagnoses after adjustment for sex, age, genotyping array, and the first 20 principle components of ancestry. Conclusion: The presence of the rs1137101 SNP for the LepR in patients in the MGI was associated with the diagnosis of bacterial pneumonia and pneumonoccal pneumonia. Additional studies will be conducted to assess the severity of illness in pneumonia associated with rs1137101 in MGI. In addition, we have generated mice with the rs1137101 mutation and will comprehensively examine the impact of this SNP on host defense in a murine model of bacterial pneumonia.

  PublisherDOI

• 2081-LB: Oxytocin Signaling in Adipocytes Is Required for Normal Milk Fat Production

  Diabetes · 2025-06-13

  article

  Introduction and Objective: Milk triglycerides, a crucial nutrient source for newborn mammals, can be derived from adipose lipolysis, diet, or de novo synthesis in mammary epithelial cells. The role of adipose lipolysis in provision of triglycerides in milk has not been well defined. Methods: To define the role of adipose lipolysis in lactation we utilized a mouse model of oxytocin receptor (OXTR) knockout specifically in adipocytes (OxtrΔAd) using an adiponectin (Adipoq) Cre. Lactation performance was characterized by profiling milk intake and composition, mammary histology and offspring growth. Group comparisons were performed using two-tailed paired or unpaired Student’s t-test as appropriate. Results: Offspring of OxtrΔAd dams lacking oxytocin receptors exhibit reduced weight gain and lower survival rates compared to offspring from WT dams (n=15-25 litters/genotype). Milk from OxtrΔAd dams was deficient in triglycerides with other milk macronutrients spared. Milk lipidomic profiling revealed reduced lipid classes including triglycerides, diglycerides, phospholipids, ceramides, and sphingomyelins. Mammary gland morphology showed a more prominent adipose fraction adjacent to the mammary epithelium, due to reduced delipidation in lactating OxtrΔAd dams. Conclusion: Oxytocin is an ancient hormone that serves critical roles in mammalian reproduction, ranging from uterine contraction to establishment of maternal behavior to induction of contraction of myoepithelial cells of the mammary ducts. Here we identify a new role for oxytocin in mediating adipose lipolysis during lactation. We further demonstrate that free fatty acids derived from lipolysis are essential for normal milk fat and offspring health. Disclosure B. Gregg: Consultant; CVS Accordant. E. Li: None. H. Sun: None. J. Aristizabal-Henao: None. M.A. Kiebish: None. D. Bridges: None. E. Rosen: Consultant; Foghorn Therapeutics. Advisory Panel; Source Bio. K. Patel: None. Funding R01DK133223

  PublisherDOI

• Harnessing Neuron-Specific Mechanisms of Autophagy as a Novel Therapeutic Intervention for Parkinson disease

  Parkinsonism & Related Disorders · 2025-04-17

  article
  PublisherDOI

• GDF15 knockout does not substantially impact perinatal body weight or neonatal outcomes in mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-03 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model ( Gdf15 -/- ) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15 -/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared to Gdf15 +/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15 -/- pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.

  PublisherOA PDFDOI

• Reduced beta-hydroxybutyrate disposal after ketogenic diet feeding in mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-18

  preprintOpen accessSenior authorCorresponding

  The ketogenic diet (KD) has garnered considerable attention due to its potential benefits in weight loss, health improvement, and performance enhancement. However, the phenotypic responses to KD vary widely between individuals. Skeletal muscle is a major contributor to ketone body (KB) catabolism, however, the regulation of ketolysis is not well understood. In this study, we evaluated how mTORC1 activation and a ketogenic diet modify ketone body disposal in muscle Tsc1 knockout (KO) mice, inbred A/J mice, and Diversity Outbred (DO) mice. Muscle Tsc1 KO mice demonstrated enhanced ketone body clearance. Contrary to expectations, KD feeding in A/J mice did not improve KB disposal, and in most strains disposal was reduced. Transcriptional analysis revealed reduced expression of important ketolytic genes in KD-fed A/J mice, suggesting impaired KB catabolism. Diversity Outbred (DO) mice displayed variable responses to KD, with most mice showing worsened KB disposal. Exploratory analysis on these data suggest potential correlations between KB disposal and cholesterol levels as well as weight gain on a KD. Our findings suggest that ketone body disposal may be regulated by both nutritional and genetic factors and these relationships may help explain interindividual variability in responses to ketogenic diets.

  PublisherOA PDFDOI

• Hippocampus Glutathione S Reductase Potentially Confers Genetic Resilience to Cognitive Decline in the AD-BXD Mouse Population

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-09 · 3 citations

  preprintOpen access

  Abstract Alzheimer’s disease (AD) is a prevalent and costly age-related dementia. Heritable factors account for 58-79% of variation in late-onset AD, but substantial variation remains in age-of- onset, disease severity, and whether those with high-risk genotypes acquire AD. To emulate the diversity of human populations, we utilized the AD-BXD mouse panel. This genetically diverse resource combines AD genotypes with multiple BXD strains to discover new genetic drivers of AD resilience. Comparing AD-BXD carriers to noncarrier littermates, we computed a novel quantitative metric for resilience to cognitive decline in the AD-BXDs. Our quantitative AD resilience trait was heritable and genetic mapping identified a locus on chr8 associated with resilience to AD mutations that resulted in amyloid brain pathology. Using a hippocampus proteomics dataset, we nominated the mitochondrial glutathione S reductase protein (GR or GSHR) as a resilience factor, finding that the DBA/2J genotype was associated with substantially higher GR abundance. By mapping protein QTLs (pQTLs), we identified synaptic organization and mitochondrial proteins coregulated in trans with a cis-pQTL for GR. We found four coexpression modules correlated with the quantitative resilience score in aged 5XFAD mice using paracliques, which were related to cell structure, protein folding, and postsynaptic densities. Finally, we found significant positive associations between human GSR transcript abundance in the brain and better outcomes on AD-related cognitive and pathology traits in the Religious Orders Study/Memory and Aging project (ROSMAP). Taken together, these data support a framework for resilience in which neuronal antioxidant pathway activity provides for stability of synapses within the hippocampus.

  PublisherOA PDFDOI

• Feasibility and acceptability of an online multicomponent very low-carbohydrate intervention in young adult women with obesity: a pilot study

  Pilot and Feasibility Studies · 2024-07-29 · 2 citations

  articleOpen access

  BACKGROUND: Approximately one-third of US young adults (18-25 years) have obesity, and there are calls to help young adults lose weight to prevent weight-related chronic conditions. This pilot trial tested the feasibility and acceptability of a very low-carbohydrate (VLC) eating pattern, with supportive positive affect and mindful eating skills, for weight management among young females with obesity. METHODS: In a single-arm trial, women (N = 17), aged 19-23, with obesity participated in a 4-month diet and lifestyle intervention. Participants were taught how to follow a VLC eating pattern with the help of a coach and 16 weekly web-based sessions. We assessed feasibility and acceptability through session participation, outcome collection, intervention satisfaction, and adverse events. RESULTS: Seventeen participants enrolled and 14 (82%) reported body weight at 4 months. Fifteen participants (94% of those beginning the intervention) viewed at least one session, and 8/15 (53%) of these participants were active in the intervention, viewing at least half of the sessions. Among the nine participants who provided 4-month self-report information, intervention satisfaction was high (mean 5.89/7, 95% CI 4.59 to 7.19). Among participants with a 4-month body weight, 7/14 (50%) lost ≥ 5% of their body weight, and of those who were also active in the intervention, 6/7 (86%) lost ≥ 5% of their body weight. There were no serious adverse events. CONCLUSIONS: The results of this pilot study suggest that a VLC eating pattern may be a feasible and acceptable approach for weight loss in some young women with obesity. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov on August 18, 2021. The trial number is NCT05010083.

  PublisherOA PDFDOI

• GDF15 Knockout Does Not Substantially Impact Perinatal Body Weight or Neonatal Outcomes in Mice

  Endocrinology · 2024-10-22 · 4 citations

  articleOpen accessSenior authorCorresponding

  Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model (Gdf15-/-) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15-/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared with Gdf15+/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15-/- pups, but this difference was no longer evident from postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.

  PublisherOA PDFDOI

• Data from The Lipid Kinase PI4KIIIβ Is Highly Expressed in Breast Tumors and Activates Akt in Cooperation with Rab11a

  2023-04-03

  preprintOpen access

  <div>Abstract<p>Emerging evidence now implicates phosphatidylinositol 4-kinases (PI4K), enzymes that generate PI(4)P from phosphatidylinositol (PtdIns), in cancer. In this study, we investigate the role of PI4KIIIβ, one of four mammalian PI4Ks, in breast cancer. Although PI4KIIIβ protein levels are low in normal breast tissue, we find that approximately 20% of primary human breast tumors overexpress it. Expression of PI4KIIIβ in breast carcinoma cells leads to increased Akt activation, dependent on increased PI(3,4,5)P<sub>3</sub> production. However, a kinase-inactive version of PI4KIIIβ also led to increased Akt activation, and no changes in PI(4)P or PI(4,5)P<sub>2</sub> lipid abundance were detected in the PI4KIIIβ-overexpressing cells. This implies that PI4KIIIβ regulates PI(3,4,5)P<sub>3</sub> and Akt independent of PI(4)P production. We find that the PI4KIIIβ-binding protein, Rab11a, a small GTPase that regulates endosomal recycling, is involved in PI4KIIIβ-mediated activation of Akt, as RNAi depletion of Rab11a impairs Akt activation. Furthermore, ectopic PI4KIIIβ expression alters cellular Rab11a distribution and enhances recruitment of PI4KIIIβ and Rab11a to recycling endosomes. This work suggests that PI4KIIIβ affects PI3K/Akt signaling through Rab11a and endosomal trafficking, independent of its lipid kinase activity. Thus, PI4KIIIβ likely plays a role in breast oncogenesis and that cooperation between Rab11a and PI4KIIIβ represents a novel Akt activation pathway. <i>Mol Cancer Res; 12(10); 1492–508. ©2014 AACR</i>.</p></div>

  PublisherDOI

Recent grants

• Regulation of Lipid Storage by mTORC1

  NIH · $1.7M · 2016–2022

Frequent coauthors

• Alan R. Saltiel

  Salk Institute for Biological Studies

  61 shared

• Innocence Harvey

  Pennington Biomedical Research Center

  55 shared

• JeAnna R. Redd

  University of Michigan–Ann Arbor

  53 shared

• Erin J. Stephenson

  35 shared

• Quynh T. Tran

  Cystic Fibrosis Foundation

  30 shared

• Irit Hochberg

  Rambam Health Care Campus

  25 shared

• Greg B. G. Moorhead

  University of Calgary

  23 shared

• Joan C. Han

  23 shared

Labs

• Bridges LabPI

  Not provided

Education

• Ph.D., Biological Sciences

  University of Calgary

  2005

• B.Sc., Biological Sciences

  University of Calgary

  2000