Fat Labs May Have A True Genetic Reason

Hello, Summarians!

Genes vs environment. Nature vs nurture. As we learn more detailed information about the genetic basis of behavior and see how it applies to the individual, we can better understand the world around us. Our lead story does just that.

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Genetic Basis for Increased Appetite and Low Metabolism in Dogs

This text discusses the role of the pro-opiomelanocortin (POMC) gene and its derivatives, particularly α-MSH, β-MSH, and β-endorphin, in regulating energy homeostasis, body weight, and feeding behaviors, emphasizing the interplay of genetic and environmental factors in obesity. The central leptin-melanocortin axis, involving hypothalamic neurons expressing POMC, is crucial for integrating systemic energy status signals, with POMC being posttranslationally modified into neuroactive peptides including α-MSH, β-MSH, and β-endorphin. These peptides modulate food intake and energy expenditure through melanocortin receptors MC3R and MC4R, with β-MSH and β-endorphin playing significant roles in energy homeostasis and feeding behavior. 

The text highlights a specific 14-base pair deletion mutation in the POMC gene in Labrador and flat-coated retriever dogs, which disrupts β-MSH and β-endorphin production without affecting α-MSH. This mutation leads to increased food motivation and altered energy expenditure in affected dogs. It serves as a natural model for studying the physiological and behavioral consequences of these peptide deficiencies. The mutation's effects on energy homeostasis are demonstrated through increased motivational salience in response to food cues and lower resting energy expenditure, implicating β-MSH's role in hunger and energy expenditure regulation, independent of α-MSH. 

Human and animal studies are discussed, showing how POMC mutations and the resulting deficiencies in α-MSH, β-MSH, and β-endorphin contribute to obesity. β-MSH is particularly highlighted for its potential physiological importance in humans, supported by evidence of its excess production in the human hypothalamus and its association with obesity when deficient. The complexity of POMC-derived peptide regulation, including their storage, trafficking, and release, is also touched upon, suggesting a nuanced understanding of their roles in energy homeostasis. 

The text concludes by noting the challenge in managing the body weight of dogs with the POMC mutation due to their increased food motivation and lower energy expenditure, alongside the speculation on molecular mechanisms underlying these phenotypic effects, such as variation in mitochondrial efficiency. This research provides valuable insights into the genetic underpinnings of obesity and the intricate mechanisms of energy balance regulation, with implications for both human and veterinary medicine. 

Marie T. Dittmann et al. Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model. Sci. Adv.10,eadj3823(2024).DOI:10.1126/sciadv.adj3823 

Bottom line — Finally a reason for these labs ;)

Biomarkers for Urinary Stones

This study investigated the metabolomic profiles of urine samples from healthy dogs and those with calcium oxalate and struvite urolithiasis to understand the metabolic changes associated with these conditions and to identify potential urinary biomarkers for distinguishing between the two types of stones. 

Key findings include: 

• Calcium oxalate urolithiasis is associated with downregulated trigonelline, suggesting its role in inhibiting stone formation. Elevated levels of (4E)-3-hydroxyhex-4-enoylcarnitine and altered phenylalanine and nicotinate metabolism were observed, indicating potential metabolic disorders and renal tubular injury in affected dogs. 

• Struvite urolithiasis showed a different metabolomic profile, with abnormalities in amino acid metabolism, particularly related to leucine, cysteine proline, and aspartate-γ-glutamate, which may reflect disturbances in renal amino acid metabolism. Urinary tract infections, common in struvite cases, were linked to changes in tryptophan metabolism and the presence of metabolites like pyocyanin. 

• Differential metabolites between calcium oxalate and struvite cases included those involved in tryptophan and arachidonic acid metabolism, suggesting potential biomarkers for distinguishing between the two stone types. 

• The study identified candidate biomarkers with potential clinical application in the precise treatment of canine urolithiasis, though it noted the limitation of not distinguishing between sterile struvite urolithiasis and UTI-associated cases. 

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Overall, this research contributes to understanding the metabolic underpinnings of canine urolithiasis and proposes urinary biomarkers for better diagnosis and treatment strategies, filling a gap in small animal clinical studies. Further validation is needed to confirm the effectiveness of these biomarkers in clinical settings. 

Xu, C., Yang, Y., Shao, Z., Ren, R., Zhang, Y., Jin, Y., & Shi, H. (2024). Candidate urinary biomarkers show promise for distinguishing between calcium oxalate versus struvite urolithiasis in dogs. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.23.09.0214 

Bottom line — Early results show some potential.

Point of Care US for Equine Emergencies

This study aimed to evaluate the impact of remote assistance on the use of point-of-care ultrasonography (POCUS) in equine emergency settings, focusing on diagnostic accuracy, clinical outcomes, and practitioner confidence. Despite demonstrating the feasibility of POCUS with remote assistance (POCUS-R) in these settings, the study faced challenges with low enrollment, which limited its ability to conclusively assess the impact on diagnostic accuracy and clinical outcomes such as the duration of sonograms and survival rates to discharge. The primary participants were house officers at a tertiary referral center, supervised by board-certified clinicians proficient in POCUS, which may have reduced the perceived need for remote assistance. 

The study found that sonogram duration was likely longer in the POCUS-R group, contributing to low enrollment. This finding echoes previous research on elective teleultrasound in horses, suggesting that in a high-volume, specialized setting, the additional time required for teleultrasound may not be justified. However, it implies that in less urgent or complex cases, or in settings with less experienced clinicians, the benefits of remote assistance could outweigh the drawbacks. 

Due to the small sample size and other limitations, such as a lack of final diagnosis for some cases and minimal inclusion of thoracic sonograms, the study could not make definitive conclusions about the diagnostic accuracy of POCUS-R or its impact on clinical outcomes. It did, however, identify a potential for teleultrasound to enhance learning, based on positive feedback from users about its educational benefits. Despite technical issues and the small image size on mobile devices, the added value of clinically useful information, reassurance for practitioners and horse owners, and educational opportunities were highlighted as significant advantages. 

The study's challenges in enrollment and adoption within a referral academic setting suggest that teleultrasound, while not likely to become routine in such environments, could be more beneficial and better received in other contexts, potentially offering significant educational value and improving accessibility and quality of training in veterinary medicine. Future research with larger sample sizes and in different settings is needed to more accurately assess the potential of teleultrasound in equine emergency care and its implications for veterinary education and practice. 

Leduc, L., Underwood, C., Stefanovski, D., Hurcombe, S., & Navas de Solis, C. (2024). Evaluation of remote assistance for point-of-care ultrasonography in a large animal hospital: a controlled randomized trial. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.23.09.0511 

Bottom line — Seems like a good idea if adopted.

Just putting things in perspective …