The obesity paradox predicts the second wave of COVID-19 to be severe in western countries

Funding Information: This work was funded by the Latvian Council of Science grants lzp-2018/1-0393 (I.A.K.), lzp-2018/2-0057 (T.K.), and lzp-2020/2-0271 (T.K.). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.While COVID-19 infection and mortality rates are soaring in Western countries, Southeast Asian countries have successfully avoided the second wave of the SARS-CoV-2 pandemic despite high population density. We provide a biochemical hypothesis for the connection between low COVID-19 incidence, mortality rates, and high visceral adiposity in Southeast Asian populations. The SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a gateway into the human body. Although the highest expression levels of ACE2 are found in people’s visceral adipose tissue in Southeast Asia, this does not necessarily make them vulnerable to COVID-19. Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs. Extra weight gained during the pandemic is expected to increase visceral adipose tissue in Southeast Asians, further decreasing the ACE2 pool. In contrast, weight gain can increase local inflammation in fat depots in Western people, leading to worse COVID-related outcomes. Because of the biological mechanisms associated with fat accumulation, inflammation, and their differential expression in Southeast Asian and Western populations, the second wave of the pandemic may be more severe in Western countries, while Southeast Asians may benefit from their higher visceral fat depots.publishersversionPeer reviewe

The Obesity Paradox Predicts the Second Wave of COVID-19 to Be Severe in Western Countries

While COVID-19 infection and mortality rates are soaring in Western countries, Southeast Asian countries have successfully avoided the second wave of the SARS-CoV-2 pandemic despite high population density. We provide a biochemical hypothesis for the connection between low COVID-19 incidence, mortality rates, and high visceral adiposity in Southeast Asian populations. The SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a gateway into the human body. Although the highest expression levels of ACE2 are found in people's visceral adipose tissue in Southeast Asia, this does not necessarily make them vulnerable to COVID-19. Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs. Extra weight gained during the pandemic is expected to increase visceral adipose tissue in Southeast Asians, further decreasing the ACE2 pool. In contrast, weight gain can increase local inflammation in fat depots in Western people, leading to worse COVID-related outcomes. Because of the biological mechanisms associated with fat accumulation, inflammation, and their differential expression in Southeast Asian and Western populations, the second wave of the pandemic may be more severe in Western countries, while Southeast Asians may benefit from their higher visceral fat depots

Extra-pair paternity explains cooperation in a bird species

In many social animals, females mate with multiple males, but the adaptive value of female extra-pair mating is not fully understood. Here, we tested whether male pied flycatchers (Ficedula hypoleuca) engaging in extra-pair copulations with neighboring females were more likely to assist their neighbors in antipredator defense. We found that extra-pair sires joined predator-mobbing more often, approached predators more closely, and attacked predators more aggressively than males without extra-pair offspring in the neighboring nest. Extra-pair mating may incentivize males to assist in nest defense because of the benefits that this cooperative behavior has on their total offspring production. For females, this mating strategy may help recruit more males to join in antipredator defense, offering better protection and ultimately improving reproductive success. Our results suggest a simple mechanism by which extra-pair mating can improve reproductive success in breeding birds. In summary, males siring extra-pair offspring in neighboring nests assist neighbors in antipredator defense more often than males without extra-pair offspring.</p

Serotoninergic Modulation of Phototactic Variability Underpins a Bet-Hedging Strategy in Drosophila melanogaster

When organisms' environmental conditions vary unpredictably in time, it can be advantageous for individuals to hedge their phenotypic bets. It has been shown that a bet-hedging strategy possibly underlies the high inter-individual diversity of phototactic choice in Drosophila melanogaster. This study shows that fruit flies from a population living in a boreal and relatively unpredictable climate have more variable variable phototactic biases than fruit flies from a more stable tropical climate, consistent with bet-hedging theory. We experimentally show that phototactic variability of D. melanogaster is regulated by the neurotransmitter serotonin (5-HT), which acts as a suppressor of the variability of phototactic choices. When fed 5-HT precursor, boreal flies exhibited lower variability, and they were insensitive to 5-HT inhibitor. The opposite pattern was seen in the tropical flies. Thus, the reduction of 5-HT in fruit flies' brains may be the mechanistic basis of an adaptive bet-hedging strategy in a less predictable boreal climate

Developmental speed affects ecological stoichiometry and adult fat reserves in Drosophila melanogaster

The elemental composition of organisms belongs to a suite of functional traits that change during development in response to environmental conditions. However, associations between adaptive variations in developmental speed and elemental body composition are not well understood. We compared body mass, elemental body composition, food uptake and fat metabolism of Drosophila melanogaster male fruit flies in relation to their larval development speed. Slowly developing flies had higher body carbon concentration than rapidly developing and intermediate flies. Rapidly developing flies had the highest body nitrogen concentration, while slowly developing flies had higher body nitrogen levels than flies with intermediate speed of development. The carbon-to-nitrogen ratio was therefore lower in rapidly developing flies than in slow and intermediate flies. We also had a group of flies grown individually and their body mass and elemental body composition were similar to those of rapidly developing individuals grown in groups. This suggests that rapid growth is not suppressed by stress. Feeding rates were lowest in the slowly developing flies. The amount of triacylglycerides was highest in the flies with intermediate developmental speed which optimizes development under many climatic conditions. Although low food intake slows down developmental speed and the accumulation of body fat reserves in slowly developing flies, their phenotype conceivably facilitates survival under higher stochasticity of their environments. Rapidly developing flies grew with less emphasis on storage build-up. Overall, this study shoes that a combination of bet-hedging, adaptive tracking and developmental plasticity enables fruit flies to respond adaptively to environmental uncertainty.</p

Analysis of Replication Intermediates Indicates That <em>Drosophila melanogaster</em> Mitochondrial DNA Replicates by a Strand-Coupled Theta Mechanism

<div><p>Mitochondrial DNA synthesis is necessary for the normal function of the organelle and for the eukaryotic organism as a whole. Here we demonstrate, using two-dimensional agarose gel electrophoresis to analyse replication intermediates, that unidirectional, strand-coupled DNA synthesis is the prevalent mode of mtDNA replication in <em>Drosophila melanogaster</em>. Commencing within the single, extended non-coding region (NCR), replication proceeds around the circular genome, manifesting an irregular rate of elongation, and pausing frequently in specific regions. Evidence for a limited contribution of strand-asynchronous DNA synthesis was found in a subset of mtDNA molecules, but confined to the ribosomal RNA gene region, just downstream of the NCR. Our findings imply that strand-coupled replication is widespread amongst metazoans, and should inform future research on mtDNA metabolism in <em>D. melanogaster</em>.</p> </div

2DNAGE of StyI- and PstI-digested mtDNA from adult flies, with explanatory drawings.

<p>Replication intermediates from adult flies digested with StyI and PstI, hybridized with probe 6. Material was further digested with S1 nuclease (panels B) or was untreated (panels A). C) Summary drawing showing major replication intermediates inferred from the gels; species are labeled as in Figs. 1 and 2. Note the fusing of two termination intermediates into a single structure due to gel compression in the PstI digest and overlapping migration patterns of dY and sz2* in the StyI digest, for similar reasons.</p

2DNAGE of mtDNA from larvae and embryos.

<p>Replication intermediates from <i>D. melanogaster</i> embryos and larvae, digested with the indicated enzymes and hybridized with probe 3. Note the rather prominent eyebrow on the Bsp1407I digest in larval mtDNA and the virtual absence of sz2 in replicating mtDNA from embryos.</p