Biology subjects

Speakman, J.

Publications and source records attributed to Speakman, J..

4 recordsLinked to original sources

bioRxiv2024

The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21

Obesity is a debilitating disease with increasing worldwide prevalence. Despite its high prevalence, specific pharmacologic intervention for obesity is challenging. Here, we report that halofuginone, an FDA-approved anti-scleroderma and anti-protozoal drug, is a promising anti-obesity agent in rodent models. Halofuginone suppressed food intake, increased energy expenditure, and resulted in weight loss in preclinical diet-induced obese mouse models, while also decreasing insulin resistance and hepatic steatosis. By combining genetic and pharmacological tools with transcriptomics, we identified that halofuginone increases FGF21 and GDF15 levels via ATF4. Using knockout mice, we show these hormones are both necessary for its anti-obesity effects. Thus, our study first reports the beneficial metabolic effects of halofuginone and underscores its utility to treat obesity and its associated metabolic complications.

pharmacology and toxicology↗

bioRxiv2023

Seasonal variation in great tit (Parus major) energy requirements: reallocation versus increased demand

Understanding how birds annually allocate energy to cope with changing environmental conditions and physiological states is a fundamental question in avian ecology. The two main hypotheses to explain annual patterns in energy use are "reallocation" and "increased demand". The reallocation hypothesis suggests equal energetic costs in winter and breeding seasons, while the increased demand suggests that energy demand should be highest during breeding. Under the standard aerobic capacity model of endothermy, birds are expected to adjust the mass and/or metabolic intensity of their bodies in ways that are consistent with expected cold- and/or activity-induced costs. Here, we look for metabolic signatures of reallocation versus increased demands in the energy requirements of a small, resident passerine of a temperate-zone (great tit, Parus major). To do so, we measured whole-body and mass-independent basal (BMR), summit (Msum), and field (FMR) metabolic rates during late winter and during the chick-rearing period (breeding). We also assessed whether, and to what extent, metabolic rates conform to the predictions of the aerobic capacity model of endothermy. We found that great tits showed no substantial differences in energy expenditure between winter and the breeding season, providing support for the reallocation hypothesis. Only mass-independent Msum showed seasonal variation, with significantly higher values ([~]4%) in winter compared to the breeding season. Our results also lend support to the predictions of the aerobic capacity model for the evolution of endothermy, as we found that whole-body BMR and Msum were positively related. We argue that both energy reallocation and the limited increase in mass-independent Msum are consistent with the relatively mild winter temperatures recorded during our study period. Our results confirm that both BMR and Msum are flexible traits that vary in ways that are consistent with expected cold- and/or activity-induced costs.

ecology↗

bioRxiv2020

A mesocosm experiment in ecological physiology: adaptive modulation of energy budget in a hibernating marsupial under chronic caloric restriction

During the last sixty years, mammalian hibernation (i.e., seasonal torpor) has been interpreted as a physiological adaptation for energy economy. However -and crucially for validating this idea - direct field comparisons of energy expenditure in hibernating and active free-ranging animals are scarce. Using replicated mesocosms and a combination of energy budgeting approaches (i.e., doubly labelled water, rates of CO2 production and food intake), we experimentally manipulated energy availability and quantified net energy costs of hibernation in a marsupial. We hypothesized that, when facing chronic caloric restriction (CCR), a hibernator should maximize torpor use for compensating the energetic deficit, compared to ad libitum fed individuals (=controls). However, intensifying torpor duration at low temperatures could increase other burdens (e.g., cost of rewarming, freezing risk). In order to explore this trade-off, we followed the complete hibernation cycle of the relict marsupial Dromiciops gliroides, and estimated its total energy requirements, and compared this with a control condition. Our results revealed: (1) that energy restricted animals, instead of promoting heat conservation strategies during hibernation (e.g., social clustering and thermoregulation), maximized torpor use and saved just enough energy to cover the deficit, and (2) that hibernation represents a net energy saving of 51% compared with animals that remained active. This work provides compelling evidence of a fine-tuning use of hibernation in response to food availability and presents the first direct estimation of energy savings by hibernation encompassing the total hibernation cycle.

ecology↗

bioRxiv2017

Food environments and obesity: cannot see the fat for the restaurants?

We recently showed that across the mainland USA there is no association between the density of fast food and full service restaurants and the prevalence of obesity. In a recent editorial it was suggested there are 4 problems with our analysis. The suggested problems were the area of analysis may not reflect adequately the exposure to different outlets, using the absolute numbers of restaurants rather than their ratio, using a global model which assumes the same relationship across all sites and finally the potential for residual confounding. In this short note we address all four of these issues and provide some new analysis of the impact of the ratio of restaurant types on obesity prevalence showing there is only a very weak association (r2 = 0.006). We conclude that none of the supposed weaknesses in our original analysis are valid.

epidemiology↗