Obesity is a major contributor to chronic health conditions, including type 2 diabetes, dyslipidaemia, cardiovascular diseases, and an increased risk of mortality. Exercise, along with food choices, impacts energy balance, but environmental factors, particularly cold temperatures, also affect obesity risk through energy expenditure (EE). Exposure to cold temperatures activates adaptive thermogenesis by starting the activation of brown adipose tissue (BAT) and other metabolic organs, resulting in increased energy expenditure.
Researchers are still investigating BAT activation variations among individuals since factors such as age body mass index (BMI) and visceral fat, as well as insulin resistance, have not been fully examined in humans. The activation of BAT, along with thermogenesis, occurs in rodents after cold exposure because prolonged cold exposure leads to brown and beige adipocyte differentiation, which improves metabolic health. Regular cold exposure treatments have been shown to activate BAT tissue in human beings, thus enhancing adipocyte regulation and insulin sensitivity. Genetic factors significantly affect BAT activity, with variations in thermogenesis-related genes shaping individual responses. Furthermore, early-life environmental exposures, including temperature during gestation, may have intergenerational effects on energy regulation and BAT activation.
Normal healthy adults participated in the study as volunteers after giving their consent to undergo both Fluorodeoxyglucose Positron Emission Tomography / Computed Tomography (FDG-PET/CT)imaging procedures and weather surveys. Information from previous studies about cold-induced thermogenesis (CIT), diet-induced thermogenesis (DIT), and total energy expenditure (TEE), along with additional data, was utilized. Each participant group was sorted according to their age and then selected from specific groups that contained physically fit subjects who did not have diabetes or substantial lifestyle risks such as heavy smoking or excessive alcohol use.
A single-cohort design included male participants aged between 18 and 29. The different research groups included male and female participants to increase universal applicability. Participation involved measuring FDG-PET/CT scans combined with near-infrared time-resolved spectroscopy (NIR-TRS) and BMI assessment, as well as body fat percentage and visceral fat determination.
An examination of cold-activated BAT involved subjecting participants to a 19°C room environment for two hours after they fasted for 12 hours. The participants received an intravenous injection of 18F-FDG after the first hour when they continued to stay in the cold environment for another hour. Total hemoglobin concentration in the supraclavicular region was measured continuously through NIR-TRS scanning for BAT activity assessment. The investigators who determined FDG-PET/CT, NIR-TRS, CIT, and DIT measurements and conducted doubly labeled water (DLW) examinations and anthropometric assessments were experienced physicians and radiologists and investigators who did not know which participants belonged to which experimental group or what the study hypothesis was. Meteorological data were measured by two research assistants who did not know about the study groups.
Both FDG-PET/CT and cold-exposure procedures were used to measure BAT functionality among 356 healthy young male volunteers who participated in Cohort 1 to study the lifelong consequences of prenatal environmental exposure. The participants experienced procedures with FDG-PET/CT during a two-hour exposure to cold temperatures (19°C).
Researchers studied two seasons as birth and fertilization times (one was cold from October 16 to April 16, the other warm from April 16 to October 16). The study found no differences between people born in winter versus summer months for BAT detection yet revealed elevated BAT activity levels (78.2% vs. 66.0%) in subjects conceived in winter (P = 0.007). BAT activity levels reached significant heights among subjects from the cold fertilization period, according to statistical analysis (P = 0.017). The birth season did not correlate with BAT activity results (P = 0.144).
The influence of fertilization season on BAT activity showed no relation to individual age, BMI, or the season of birth, as determined by the adjusted odds ratio (OR) value of 1.949 (P = 0.007). The cold fertilization approach increased BAT activity in different parts of the body, including the thoracic area combined with the cervical and axillary areas, as well as the mediastinal and perirenal areas. BAT, which becomes active in cold temperatures, serves as the basis for non-shivering CIT to regulate energy expenditure.
Research investigators studied the effects of fertilization season on CIT as a variable among 42 young male study participants (Cohort 3). The research conducted under the study revealed no meaningful differences between cold and warm birth season groups in BAT activity measurement results (P > 0.05). DIT and postprandial thermogenesis levels were higher in cold-fertilized participants when compared to the warm-fertilized group at P = 0.012. According to research, the cool months of fertilization show increases in adaptive thermogenesis, which helps confirm the genetic propagation of BAT activation.
References: Yoneshiro T, Matsushita M, Fuse-Hamaoka S, et al. Pre-fertilization-origin preservation of brown fat-mediated energy expenditure in humans. Nat Metab. 2025. doi:10.1038/s42255-025-01249-2
