Temperature has a profound effect on many aspects of murine physiology. This raises the question of the best temperature at which mice should be housed to maximize the translational potential to ...humans. The temperatures at which mice have been routinely kept for studies of molecular physiology (20-21 °C) maximize the comfort of animal handling staff. There is a widespread movement suggesting we should perform experiments instead on mice housed at 30 °C. This often produces very different outcomes. Here we analyze the basis of this suggestion and show that while 20-21 °C is too cold, 30 °C is probably too hot. Rather we suggest an intermediate temperature "the Goldilocks solution" of 25-26 °C is probably optimal. This should be combined with providing animals with nesting material so that they can construct nests to generate microclimates that are within their own control. Providing copious nesting material has additional spin-off advantages in terms of increasing environmental enrichment. Ultimately, however, advocating a single temperature to mimic human physiology is plagued by the problem that humans vary widely in the temperature environments they experience, with consequences for human disease. Hence studying responses at a range of temperatures may provide the greatest insights and translational potential.
The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged ...5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda–unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.
Summary
The disposable soma hypothesis explanation of the effects of caloric restriction (CR) on lifespan fails to explain why CR generates negative impacts alongside the positive effects and does ...not work in all species. I propose here a novel idea called the clean cupboards hypothesis which overcomes these problems.
Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT ...also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.
Cold exposure stimulates energy expenditure and glucose disposal. If these factors play a significant role in whole body energy balance, and glucose homeostasis, it is predicted that both obesity and ...type 2 diabetes prevalence would be lower where it is colder. Previous studies have noted connections between ambient temperature and obesity, but the direction of the effect is confused. No previous studies have explored the link of type 2 diabetes to ambient temperature. We used county level data for obesity and diabetes prevalence across the mainland USA and matched this to county level ambient temperature data. Average ambient temperature explained 5.7% of the spatial variation in obesity and 29.6% of the spatial variation in type 2 diabetes prevalence. Correcting the type 2 diabetes data for the effect of obesity reduced the explained variation to 26.8%. Even when correcting for obesity, poverty and race, ambient temperature explained 12.4% of the variation in the prevalence of type 2 diabetes, and this significant effect remained when latitude was entered into the model as a predictor. When obesity prevalence was corrected for poverty and race the significant effect of temperature disappeared. Enhancing energy expenditure by cold exposure will likely not impact obesity significantly, but may be useful to combat type 2 diabetes.
Abstract
Calorie restriction (CR) extends life span by modulating the mechanisms involved in aging. We quantified the hepatic proteome of male C57BL/6 mice exposed to graded levels of CR (0%–40% CR) ...for 3 months, and evaluated which signaling pathways were most affected. The metabolic pathways most significantly stimulated by the increase in CR, included the glycolysis/gluconeogenesis pathway, the pentose phosphate pathway, the fatty acid degradation pathway, the valine, leucine, and isoleucine degradation pathway, and the lysine degradation pathway. The metabolism of xenobiotics by cytochrome P450 pathway was activated and feminized by increased CR, while production in major urinary proteins (Mups) was strongly reduced, consistent with a reduced investment in reproduction as predicted by the disposable soma hypothesis. However, we found no evidence of increased somatic protection, and none of the 4 main pathways implied to be linked to the impact of CR on life span (insulin/insulin-like growth factor IGF-1, nuclear factor-κB NF-κB, mammalian Target of Rapamycin mTOR, and sirtuins) as well as pathways in cancer, were significantly changed at the protein level in relation to the increase in CR level. This was despite previous work at the transcriptome level in the same individuals indicating such changes. On the other hand, we found Aldh2, Aldh3a2, and Aldh9a1 in carnitine biosynthesis and Acsl5 in carnitine shuttle system were up-regulated by increased CR, which are consistent with our previous work on metabolome of the same individuals. Overall, the patterns of protein expression were more consistent with a “clean cupboards” than a “disposable soma” interpretation.
Although it is widely accepted that obesity results from an imbalance of energy intake and expenditure, the mechanisms underlying this process and effective strategies for prevention and treatment ...are unclear. Growing evidence suggests excess consumption of sugar may play an important role, yet we showed previously in mice that consuming up to 30% of calories as sucrose in the diet had no impact on weight regulation. Since in humans consumption of sugar-sweetened beverages has been widely implicated, we investigated whether the mode of ingestion (solid or liquid) had different impacts on body weight regulation and glucose homeostasis.
Dietary sucrose was delivered in solid (as part of a standard pelleted rodent chow) and liquid (in drinking water) to C57BL/6 mice for 8 weeks. Body weight, body composition, energy intake and expenditure were monitored, as well as glucose and insulin tolerance tests. Expression of sweet taste receptors on the tongue, and glycogen and fat contents of the liver were also measured.
Consumption of sucrose-sweetened water, but not equivalent levels of solid sucrose, led to body fat gain in C57BL/6 mice. Glucose intolerance was positively correlated to body fatness, rather than sucrose intake.
Our data support the suggestion that consumption of liquid sucrose may be an important contributor to dysregulation of body weight and related metabolic syndromes.
•Liquid sucrose intake was associated with increased energy consumption and greater body fat gain.•The same level of sucrose in a solid diet did not lead to higher energy intake or elevated body weight and fatness.•Elevated adiposity was correlated with impairment of glucose homeostasis and insulin resistance.•Glucose homeostasis and insulin resistance were related to adiposity and the mode but not the level of sucrose intake.
The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or ...20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.
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•Very low protein caused decreased body fat and improved glucose tolerance•Fatty acid and amino acid metabolism were changed by dietary low protein•The 1% protein group did not show hyperphagia despite the hunger pathway being activated•The effect of 1% protein on food intake was linked to hypothalamic mTOR signaling
Wu et al. investigated how very low levels of dietary protein affect energy balance by exposing mice to diets containing 1%–20% protein. Very low protein caused decreased food intake despite activated hunger signaling and led to decreased body weight, partially due to inhibited hypothalamic mTOR signaling but not eIF2a, TRPML1, and FGF21 signaling.
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