S2E6: What color is your fat?

The word fat evokes a certain reaction in our culture. For associate professor of neurobiology Kristy Townsend and her students it’s the subject of research on many levels. Fat communicates with the brain, it battles disease, it plays a role in the aging process. It also comes in a variety of colors with differing functions. Townsend talks about her work on this connection and how it relates to obesity and diabetes — diseases that are becoming pandemics. She also talks about the role of basic research and the growing biotech industry in Maine

Brown adipose tissue

Obesity is currently a global pandemic, and is associated with increased mortality and co-morbidities including many metabolic diseases. Obesity is characterized by an increase in adipose mass due to increased energy intake, decreased energy expenditure, or both. While white adipose tissue is specialized for energy storage, brown adipose tissue has a high concentration of mitochondria and uniquely expresses uncoupling protein 1, enabling it to be specialized for energy expenditure and thermogenesis. Although brown fat was once considered only necessary in babies, recent morphological and imaging studies have provided evidence that, contrary to prior belief, this tissue is present and active in adult humans. In recent years, the topic of brown adipose tissue has been reinvigorated with many new studies regarding brown adipose tissue differentiation, function and therapeutic promise. This review summarizes the recent advances, discusses the emerging questions and offers perspective on the potential therapeutic applications targeting this tissue

Simulated climate change impacts on striped bass, blue crab and Eastern oyster in oyster sanctuary habitats of Chesapeake Bay

Oyster reefs and the species that inhabit them will likely be impacted by shifts in environmental conditions due to climate change. This study examined the potential impact of long-term shifts in water temperature and salinity as a result of climate change on the biomasses of important fisheries species within oyster sanctuary sites in the Choptank and Little Choptank river complex (CLC) in Chesapeake Bay using an Ecopath with Ecosim food web model. The model was used to evaluate changes in the oyster reef food web, with particular emphasis on impacts to striped bass (Morone saxatilis), blue crab (Callinectes sapidus), and Eastern oysters (Crassostrea virginica). Eight different climate change scenarios were used to vary water temperature and salinity within Chesapeake Bay up to the year 2100 based on projections given by previous studies. Simulations used a 4 °C increase in temperature along with an increase (+12 or +10) or decrease (−2) in salinity at annual time steps. The rate of change in species biomasses across scenarios ranged from −0.0052 to 0.0008 t/km2/month for striped bass, −0.0021 to 0.0026 t/km2/month for blue crab and −0.0018 to 0.0026 t/km2/month for oysters. Across the majority of scenarios, the biomasses of striped bass and blue crab decreased, while oyster biomass increased. These results begin to offer insight on the interaction between oyster reef restoration benefits and climate change. The modeling framework utilized by this study may be adapted to other systems to assess the effects of climate change on other coastal restoration habitats

The involvement of neuroimmune cells in adipose innervation.

BACKGROUND: Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and \u27browning\u27 of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration, and plasticity, including neurite outgrowth and synapse formation. Peripheral immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose SVF secretes brain derived neurotrophic factor (BDNF). METHODS: We now show that deletion of this neurotrophic factor from the myeloid lineage of immune cells led to a \u27genetic denervation\u27 of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. RESULTS: We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C CONCLUSIONS: We propose that these myeloid lineage, cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure

Brown Fat Paucity Due to Impaired BMP Signaling Induces Compensatory Browning of White Fat

Summary Maintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation1. Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans2-5, BAT holds great promise for the treatment of obesity and metabolic syndrome1. Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the interscapular region of mice, and the recruitable BAT (rBAT) that resides within white adipose tissue (WAT)6 and skeletal muscle7, that has alternatively been called beige8, brite9, or inducible BAT10. Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT10-12. We here provide evidence for a systemically active regulatory mechanism that serves to control whole body BAT-activity for thermoregulation and energy homeostasis. Genetic ablation of type 1A BMP-receptor (Bmpr1A) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between the constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease

A scoping review of antimicrobial resistance in the Australian dairy cattle industry

INTRODUCTION: Quantification of antimicrobial resistance (AMR) is beneficial to inform policies and direct prudent antimicrobial use. AIM: This study aimed to assess the current published evidence of AMR from passive and active ad hoc surveillance activities within the Australian dairy cattle industry. METHODS: Following a scoping review framework 373 articles published before January 2023 were retrieved using the keyword search function from two online databases (PubMed® and Web of Science™ Core Collection). The duplicate articles were removed and the title, abstract, and full text of the remaining articles were reviewed following the study objectives and inclusion criteria (location, subject/theme, and data). Data from the remaining articles were extracted, summarised, interpreted and the study quality assessed using the Grades of Recommendations, Assessment, Development, and Evaluation guidelines. RESULTS: A total of 29 articles dating from the 1960 s until 2022 were identified to meet the study criteria (passive: n = 15; active: n = 14). Study characteristics such as sampling type, sampling method, and AMR assessment were all common characteristics from both passive and active surveillance articles, being milk samples, individual sampling, and phenotypic assessment respectively. Passive surveillance articles had a wider range in both the type of bacteria and the number of antimicrobials investigated, while active surveillance articles included a higher number of bacterial isolates and sampling from healthy populations. There was an overall low level of clinical AMR across all articles. Higher prevalence of non-wildtype Escherichia coli, Salmonella spp., and Staphylococcus spp., although limited in data, was suggested for commonly used Australian veterinary antimicrobials for these bacteria. The prevalence of phenotypic AMR varied due to the health and age status of the sampled animals. The articles reviewed in this study suggest the prevalence of AMR genes was higher for commonly used antimicrobials, although genes were not always related to the phenotypic AMR profile. CONCLUSIONS: Published evidence of AMR in the Australian dairy cattle industry is limited as demonstrated by only 29 articles included in this review following selection criteria screening. However, collectively these articles provide insight on industry AMR prevalence. For example, the suggestion of non-wildtype bacteria within the Australian dairy cattle indicating a risk of emerging or increasing industry AMR. Therefore, further surveillance is required to monitor the development of future AMR risk within the industry. Additionally, evidence suggesting that animals varying in health and age differ in prevalence of AMR imply a requirement for further research into animal population demographics to reduce potential bias in data collated in both national and global surveillance activities

Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance

SUMMARY Obesity develops due to altered energy homeostasis favoring fat storage. Here we describe a novel transcription co-regulator for adiposity and energy metabolism, TRIP-Br2 (also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of the knockout (KO) mice exhibited greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The KOs also exhibit higher energy expenditure due to increased adipocyte thermogenesis and oxidative metabolism by up-regulating key enzymes in respective processes. Our data show for the first time that a cell cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data together with the observation that TRIP-BR2 expression is selectively elevated in visceral fat in obese humans suggests that this transcriptional co-regulator is a novel therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia

Actionable Patient Safety Solutions (APSS) #6: Hand-off Communications

Hand-off communications, or hand-off processes, involve the transition of care as well as the transfer of patient-specific information by one healthcare professional to another with the purpose of providing a patient with safe, continuous care. A successful hand-off can only be achieved by effective communication

Clonal analyses and gene profiling identify genetic biomarkers of human brown and white preadipocyte thermogenic potential

Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generated clones of brown and white preadipocytes from human neck fat of four individuals and characterized their adipogenic differentiation and thermogenic function. Combining an uncoupling protein 1(UCP1) reporter system and expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated in culture. Knocking out the positive UCP1 regulators identified by this approach, PREX1 and EDNRB in brown preadipocytes using CRISPR/Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer the identification of possible biomarkers of thermogenically competent preadipocytes