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Genetic factors are believed to be primarily responsible for obesity; however, an understanding of how genes for obesity have become so prevalent in modern society has proved elusive. Several theories have attempted to explain the genetic basis for obesity, but none of these appear to factor in the interethnic variation in obesity. Emerging evidenc...
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... for a single gene or allele to strongly influence adiposity and cold adaption simultaneously, BAT thermogenesis must be a leading candidate in their combined causality. Genetic variants that have a strong association with BMI and latitude and that have been shown to function in BAT/NST are highlighted in Table 1. A study revealed that BAT volume and NST were reduced in south Asians, which had a negative impact on basal metabolism and energy expenditure [52]. ...Citations
... These diverse adaptation patterns are influenced by factors including cold stress intensity, hormonal fluctuations, physical attributes, and dietary practices that have shaped and continue to shape our evolutionary history. Although several polymorphisms have been proposed as candidates for carriers of cold adaptation through NST (59,64), it may be that the Jomon lineage represents the first instance where signals of cold adaptation through NST have been polygenically detected, observed consistently across multiple loci. ...
Previous genomic studies understanding the dispersal of Homo sapiens have suggested that present-day East Eurasians and Native Americans can trace their ancestry to migrations from Southeast Asia. However, ineluctable adaptations during the Last Glacial Maximum (LGM) remain unclear. By analyzing 42 genomes of up to 30-fold coverage from prehistoric hunter-gatherers, Jomon, we reveal their descent from Upper Paleolithic (UP) foragers who migrated to and isolated in the Japanese archipelago during Late Pleistocene. We provide compelling evidence suggesting that these UP people underwent positive selection for cold environments, aiding their survival through the LGM facilitated by non-shivering thermogenesis and detecting it polygenically across multiple loci in the Jomon lineage. Our study pioneers the close estimation of the physiological adaptation of ancient humans by the paleogenomic approach.
... One other reason contributing to the relative lower energy expenditure at rest, besides higher percentages of body fat, amongst South Asians is the lower amount of brown adipose tissue (BAT, or brown fat) [69,73]. BAT is a type of adipose tissue that is specialized for heat generation and can be responsible for up to 20% of total energy expenditure in its activated mode [74]. ...
... For South Asians this means a reduced capacity to generate nonshivering thermogenesis or waste heat [69]. In cold-adapted populations, higher levels of BAT are protective for cardiometabolic health (including diabetes), as BAT produces uncoupled mitochondrial respiration for heat generation that burns off excess calories (nonshivering thermogenesis) [73]. The protective mechanism likely involves the use of BAT burn or its metabolism of excess calories in states of caloric overabundance [73,75]. ...
... In cold-adapted populations, higher levels of BAT are protective for cardiometabolic health (including diabetes), as BAT produces uncoupled mitochondrial respiration for heat generation that burns off excess calories (nonshivering thermogenesis) [73]. The protective mechanism likely involves the use of BAT burn or its metabolism of excess calories in states of caloric overabundance [73,75]. ...
South Asians, representing one quarter of the world's population, have disproportionally high rates of obesity and cardiometabolic disease thus resulting an epidemic health crisis. This crisis could be the consequence of epigenetic effects exacerbated during the colonial-era famines resulting in a unique starvation-adapted physiology. Due to evolutionary mismatch in circumstances of abundance, this starvation-adapted physiology can become harmful. Evidence for this starvation adaptation in South Asians includes high body fat and unfavorable adipokines; low lean body mass; lower resting energy expenditure (compounded by lack of brown adipose tissue); greater insulin resistance and insulin response; exaggerated lipemic response to fat and sugar intake; less capacity to handle an overabundance of food; lower fat burning (oxidative capacity) and VO2max during aerobic exercise; and energy-conserving response to resistance exercise, as well as increased lipoprotein (a) levels. The Roma people, also of South Asian ancestry, may represent an interesting pre-colonial historical control. Physician and patient knowledge of this unique physiology in South Asians will promote a stronger physician-patient relationship and foster compliance with treatment.
... Multiple lines of evidence from evolutionary history, genetic and twin studies, support a genetic basis for obesity and differences in obese and lean phenotypes in women with PCOS [183][184][185][186]. The majority of women with PCOS are overweight or obese, with reports ranging from 38-88% [152,186]. ...
Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean
phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine-disrupting chemical exposure, and the influence of lifestyle factors such as poor-quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.
... Multiple lines of evidence from evolutionary history, genetic and twin studies, support a genetic basis for obesity and differences in obese and lean phenotypes in women with PCOS (182)(183)(184)(185). The majority of women with PCOS are overweight or obese, with reports ranging from 38-88% (151,185). ...
Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.
... Subsequently to the dispersal of Homo sapiens out of Africa during the Paleolithic [1], human populations required adaptations to diverse climatic conditions [2] achieved through morphological and cultural adjustments and metabolic mutations [3], such as brown adipose tissue (BAT) upregulation in cold climates [4]. The interest in understanding the mechanisms of cold adaptation comes both from obvious anthropological and evolutionary implications, and from theories that attribute to populations with higher BAT activity an increased resistance to obesity and diabetes [5]. When Europeans reached Tierra del Fuego in 1520, it was inhabited by different populations (mostly named Yamana, Alacaluf and Ona) generally grouped under the term Fuegians, today extinct [6]. ...
The Fuegians, extinct inhabitants of Tierra del Fuego, were an exemplary case of a cold-adapted population capable of living in extreme weather conditions without any adequate clothing, however the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in BAT-expressing modern humans of temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection of their skeletons against major cold-related damage. Our results increase our understanding of how ecological challenges have been important drivers of genetic and environmental factors interactions.
... The brown adipocytes are multilocular and contain less lipid. [19]. Recently, it has been shown that the brown adipose tissue could be increased with the catecholamine discharge. ...
... Biologically, humans are prone to conserve body fat as a defense mechanism in case of starvation and famine. The theory of "thrifty gene" claimed that human genes were predisposed to accumulate adipose tissue for use in case of energy requirement [1,11,19]. This mechanism was a key factor for survival once. ...
... European Americans or East Asian Americans, have a lower obesity burden. 5 In fact, there is evidence of selection by climate across the genome, 6 and specifically in genes related to the non-shivering thermogenesis of brown adipose tissue (BAT) like those encoding the uncoupling proteins (i.e. UCP1-3) or the leptin receptor (LEPR). ...
... For example, caloric intake recommendations may want to take differences in RMR across ancestral populations into account. 5 Thus, taking an evolutionary perspective to the study of obesity may shed light on the role of evolutionary trade-offs and mismatches in both clinical care and global health. ...
Obesity is a pandemic that has increased exponentially during the past decades due in large part to recent changes in lifestyle and food delivery systems. Yet, there is still a great variability in the burden of obesity across ancestral populations. For example, in the United States (US) prevalence estimates of adult obesity vary from 13% to 48% in Asian Americans and African Americans [1]. Such variable observations within the same obesogenic environment have motivated a wide array of inquiry into the genetic, epigenetic and social determinants of obesity, and their complex interactions with modern lifestyles and food systems.
This chapter describes the current understanding of climate and human variation using global and local approaches, and considers the emerging topics of epigenetic analyses and climate change. It characterizes stresses, describes human biological variation, and presents evidence for modes of adaptation. Anthropologists operationalize climate broadly to include temperature and humidity, ultraviolet radiation (UVR) intensity, and altitude above sea level. Thermoneutrality refers to the ambient temperature at which a nude, inactive adult maintains core temperature without engaging behavioral and biological thermoregulation. UVR penetrates the outer layers of the skin, where melanin and other molecules either reflect or absorb radiation. Climate change will alter the water supply for human and agricultural use, including precipitation, ground, and surface sources; “the quantity and quality of our water are woven into the intersections between human health, culture, and human biology, just as they are for food”.
The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human–environment interactions during Humankind history.
Nonshivering thermogenesis (NST) is a key mechanism that allows mammals to control their body temperature. Sex can frequently affect thermoregulatory requirements; therefore, males and females can be expected to differ significantly in their NST capacity. Several sex-related differences in NST have been described in laboratory animals and humans; however, these parameters are relatively rarely studied in animals living under natural conditions. Here, I briefly review factors that may be responsible for this disparity and point out two situations that should be particularly promising in searching for sex differences in NST under natural conditions: the lactation period and potential mitonuclear conflicts over NST control in species with genetic polymorphism.
