1. As a first approximation, whole-body metabolic rate can be considered as the sum of metabolic rates of constituent cells. Yet, among several current explanations of metabolic rate scaling, only two explicitly invoke cell architecture of organisms: (1) the Metabolic Theory of Ecology, which predicts size invariance of metabolically active cells, such as erythrocytes and (2) the cell metabolism hypothesis postulating partial dependence of metabolic scaling on the cell size (CS), which is mediated by nucleus/genome size variation. 2. Here, we tested (1) and (2) by comparing standard metabolic rate (SMR), erythrocyte size (used as a proxy of CS) and nucleus size (NS) between diploid and triploid individuals of a small fish (body mass of c. 3 g) belonging to the Cobitis taenia hybrid complex. 3. We demonstrated a positive correlation of CS with genome/nucleus size and an inverse relationship between those traits and SMR. SMR scaled to body mass with a 0·92 ± 0·05 exponent, which significantly differed from the ¾ value, while CS scaled with body mass with an allometric exponent of 0·05 ± 0·007, which significantly differed from 0. Ploidy level explained c. 85% of CS variation. 4. Our results provide empirical support for CS and genome/nucleus size being important determinants of metabolic rate variation and consequently, its allometric scaling. They call attention to the significance of a long-neglected integration of cellular and organismal perspectives in studies of body size–metabolic rate relationships and their consequences for energy utilization in the wild.

Introduction: Identification of physiological factors influencing susceptibility to insulin resistance and type 2 diabetes (T2D) remains an important challenge for biology and medicine. Numerous studies reported energy expenditures as one of those components directly linked to T2D, with noticeable increase of basal metabolic rate (BMR) associated with the progression of insulin resistance. Conversely, the putative link between genetic, rather than phenotypic, determination of BMR and predisposition to development of T2D remains little studied. In particular, low BMR may constitute a considerable risk factor predisposing to development of T2D. Research design and methods: We analyzed the development of insulin resistance and T2D in 20-week-old male laboratory mice originating from three independent genetic line types. Two of those lines were subjected to divergent, non-replicated selection towards high or low body mass-corrected BMR. The third line type was non-selected and consisted of randomly bred animals serving as an outgroup (reference) to the selected line types. To induce insulin resistance, mice were fed for 8 weeks with a high fat diet; the T2D was induced by injection with a single dose of streptozotocin and further promotion with high fat diet. As markers for insulin resistance and T2D advancement, we followed the changes in body mass, fasting blood glucose, insulin level, lipid profile and mTOR expression. Results: We found BMR-associated differentiation in standard diabetic indexes between studied metabolic lines. In particular, mice with low BMR were characterized by faster body mass gain, blood glucose gain and deterioration in lipid profile. In contrast, high BMR mice were characterized by markedly higher expression of the mTOR, which may be associated with much slower development of T2D. Conclusions: Our study suggests that genetically determined low BMR makeup involves metabolism-specific pathways increasing the risk of development of insulin resistance and T2D.

Carcinogenesis is one of the leading health concerns afflicting presumably every single animal species, including humans. Currently, cancer research expands considerably beyond medicine, becoming a focus in other branches of natural science. Accumulating evidence suggests that a proportional scale of tumor deaths involves domestic and wild animals and poses economical or conservation threats to many species. Therefore, understanding the genetic and physiological mechanisms of cancer initiation and its progression is essential for our future action and contingent prevention. From this perspective, I used an evolutionary-based approach to re-evaluate the baseline for debate around Peto’s paradox. First, I review the background of information on which current understanding of Peto’s paradox and evolutionary concept of carcinogenesis have been founded. The weak points and limitations of theoretical modeling or indirect reasoning in studies based on intraspecific, comparative studies of carcinogenesis are highlighted. This is then followed by detail discussion of an effect of the body mass in cancer research and the importance of cell size in consideration of body architecture; also, I note to the ambiguity around cell size invariance hypothesis and hard data for variability of cell size across species are provided. Finally, I point to the new research area that is driving concepts to identify exact molecular mechanisms promoting the process of tumorigenesis, which in turn may provide a proximate explanation of Peto’s paradox. The novelty of the approach proposed therein lies in intraspecies testing of the effect of differentiation of cell size/number on the probability of carcinogenesis while controlling for the confounding effect of body mass/size.

Cardiovascular diseases (CVD) are one of the most common causes of mortality likely genetically linked to the variation in basal metabolic rate (BMR). A robust test of the significance of such association may be provided by artificial selection experiments on animals selected for diversification of BMR. Here we asked whether genetically determined differences in BMR correlate with anatomical shift in endothelium structure and if so, the relaxation and contraction responses of the aorta in mice from two lines of Swiss-Webster laboratory mice (Mus musculus) divergently selected for high or low BMR (HBMR and LBMR lines, respectively). Functional and structural study of aorta showed that a selection for divergent BMR resulted in the between-line difference in diastolic aortic capacity. The relaxation was stronger in aorta of the HBMR mice, which may stem from greater flexibility of aorta mediated by higher activity of Ca²⁺-activated K⁺ channels. Structural examination also indicated that HBMR mice had significantly thicker aorta's middle layer compared to LBMR animals. Such changes may promote arterial stiffness predisposing to cardiovascular diseases. BMR-related differences in the structure and relaxation ability of aortas in studied animals may be reminiscent of potential risk factors in the development of CVD in humans.

There is a large diversity of red blood indices determining oxygen transport ability in vertebrates. In fish this diversity is particularly large, probably due to the great variability in water environments, which impedes the possibility of finding and understanding general patterns. It has been assumed that in mammals, the measure determining the ability of a blood unit to transport oxygen is the ratio of hemoglobin concentration (HB) and total erythrocyte surface area (TSAE). It was also shown that both in mammals and birds the amount of hemoglobin per total surface area unit (Hb/ TSAE) conditions maximum use of respiratory pigment in oxygen transport, in different physiological and environmental conditions. In order to check whether this regularity occurs in fish, red blood indices were analyzed in seven species of freshwater fish, differing noticeably in their biology and body mass in two seasons of the year. Notwithstanding this marked seasonal variability to the component variables together determining the total surface area of erythrocytes, the value for TSAE was found to differ in proportion to the higher or lower concentrations of HB. In consequence, the HB/TSAE ratio indicative of the maximal use of haemoglobin in the transport of oxygen was constant in all of the fish studied between analyzed seasons. This constancy resembling that to be noted in birds is most probably related to the counter-current gaseous exchange ongoing in the gills of fish.