SummarySequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the β-MSH and β-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
Hypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release g-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic a-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior.
We evaluated coxofemoral joints from museum specimens of: Vulpes lagopus; Vulpes vulpes; Vulpes velox; Nyctereutes procyonoides; Urocyon cinereoargenteus; Aenocyon [Canis] dirus; Canis latrans; Canis lupus lupus; Canis lupus familiaris; C. l. familiaris × latrans; and Canis dingo. Acetabular components included: fossa; articular surface; medial and lateral articular margins; and periarticular surfaces. Acetabular components variably revealed: osteophyte‐like features; varying appearance of articular margin rims (especially contour changes); rough bone surfaces (especially fossa and articular surface); and surface wear. Proximal femoral components included: articular surface; articular margin; periarticular surfaces; and joint capsule attachment. Femoral components variably revealed: rough bone surface; bone loss; articular margin osteophyte‐like features; caudal post‐developmental mineralized prominence; and enthesophytes along the joint capsule attachment. Non‐metric multidimensional scaling was used to analyze right–left asymmetric relationships between observed traits, across taxa. Significantly different acetabular trait asymmetry involved only C. latrans—C. l. familiaris; V. vulpes—N. procyonoides, and U. cinereoargenteus—N. procyonoides. There were no significant lateralized differences in proximal femoral traits involving modern canids, ancient and modern C. l. familiaris, or modern vulpines. Thus, the observations were strongly bilateral. We hypothesized high similarity of traits across taxa. The data confirm the hypothesis and strongly suggest broad and deep morphological and mechanistic conservation that almost certainly pre‐existed (at least) all modern canids. Further zoological studies are needed to evaluate phylogenic implications in greater detail.
We examined scapula glenoids (n = 14) and proximal articular humeri (n = 14) of seven gray wolves that were maintained in a sanctuary park setting. Immediately after death, observations were made visually in situ and by radiography. Further observations were made in a museum laboratory setting, prior to and following clearing of soft tissues. Selected dry bone specimens were evaluated using computed tomography. Significant cartilage erosion and osteoarthropathy were identified in all shoulder joints. No single evaluation method yielded maximal information. Plain film radiography revealed only more severe changes. Computed tomography yielded more detail and clarity than standard radiography. Direct examination of articular cartilage informed about joint soft tissue, and dry bone informed about externally visible bone pathology. These data provide a basis for biological, biomedical, ecological, and archaeological scientists to improve retrospective interpretations of bone lesions. They further support developing plausible differential diagnoses for features of ancient and modern animal bones. We noted a dog-like capacity for wolf longevity in a non-free-roaming environment. However, aged wolves' life spans far exceeded those of similar-sized domestic dogs and breeds, suggesting the possibility of an important species difference that should be explored. We suggest also a hypothesis that the driving force for joint pathology in sheltered non-domestic species may relate significantly to achieving the longevity that is possible biologically, but is uncommon in the wild because of differential stochastic influences. Anat Rec, 299:1338-1347, 2016. © 2016 Wiley Periodicals, Inc.
Hypothalamic Pro-opiomelanocortin (POMC) neurons are classically known to trigger satiety. However, they encompass heterogeneous subpopulations whose functions are unknown.Here we show that POMC neurons releasing GABA, glutamate or both neurotransmitters possess distinct spatial distribution, molecular signatures and functions. Functional specificity of these subpopulations relies on the energy sensor mechanistic Target of Rapamycin Complex 1 (mTORC1), since pharmacological blockade of mTORC1, by mimicking a cellular negative energy state, simultaneously inhibited POMC/glutamatergic and activated POMC/GABAergic neurons. Chemogenetics and conditional deletion of mTORC1 then demonstrated that mTORC1 blockade in POMC neurons causes hyperphagia. This is due to decreased POMCderived anorexigenic a-melanocyte-stimulating hormone and the recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Genetic inhibition of glutamate release from POMC neurons also produced hyperphagia, recapitulating the phenotype caused by mTORC1 blockade.Altogether, these findings pinpoint the molecular mechanisms engaged by POMC neurons to oppositely control feeding, thereby challenging conventional views about their functions.
Diseases of two very old red foxes Lawler et al.
The growth and development of the corpus luteum (CL) is regulated by gonadotropic hormones. It is formed by granulosa cells (GCs), theca cells, and endothelial cells, and is the primary source of circulating progesterone. During early pregnancy only human chorionic gonadotropin (hCG) but not luteinizing hormone (LH) extends the life span of the CL, although hCG and LH interact with the same receptor and have similar actions on the CL. In this study a recently by our group established spheroidal GC culture assay served as a model of CL development on which we compared the actions of the gonadotropic hormones LH and hCG. To find out which signal pathways take part in the hormonal regulation of GC we stimulated GC-spheroids with modulators of protein kinases A and C dependent signaling cascades and determined their impact on sprout forming activity in GC. Our results indicate that PKA-dependent signaling pathways play a major role in mediating the hormonal-induced signaling cascades leading to sprouting in GC. Furthermore, this study strongly indicates that the different effects of hCG and LH in the maintenance of the CL may be reasoned in different signal transduction pathways triggered by hCG or LH.
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