Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise.

Poor maternal diet can lead to metabolic disease in offspring, whereas maternal exercise may have beneficial effects on offspring health. In this study, we determined ifmaternal exercise could reverse the detrimental effects of maternal high-fat feeding on offspring metabolism of female mice. C57BL/6 female mice were fed a chow (21%) or high-fat (60%) diet and further divided by housing in static cages or cages with running wheels for 2 weeks prior to breeding and throughout gestation. Females were bred with chow-fed sedentary C57BL/6 males. High fat–fed sedentary dams produced female offspring with impaired glucose tolerance compared with offspring of chow-fed dams throughout their first year of life, an effect not present in the offspring from high fat–fed dams that had trained. Offspring from high fat–fed trained dams had normalized glucose tolerance, decreased fasting insulin, and decreased adiposity. Liver metabolic function, measured by hepatic glucose production in isolated hepatocytes, hyperinsulinemic-euglycemic clamps, liver triglyceride content, and liver enzyme expression, was enhanced in offspring from trained dams. In conclusion, maternal exercise negates the detrimental effects of a maternal high-fat diet on glucose tolerance and hepatocyte glucose metabolism in female offspring. The ability of maternal exercise to improve the metabolic health of female offspring is important, as this intervention could combat the transmission of obesity and diabetes to subsequent generations.

SummaryExercise affects whole-body metabolism through adaptations to various tissues, including adipose tissue (AT). Recent studies investigated exercise-induced adaptations to AT, focusing on inguinal white adipose tissue (WAT), perigonadal WAT, and interscapular brown adipose tissue (iBAT). Although these AT depots play important roles in metabolism, they account for only ∼50% of the AT mass in a mouse. Here, we investigated the effects of 3 weeks of exercise training on all 14 AT depots. Exercise induced depot-specific effects in genes involved in mitochondrial activity, glucose metabolism, and fatty acid uptake and oxidation in each adipose tissue (AT) depot. These data demonstrate that exercise training results in unique responses in each AT depot; identifying the depot-specific adaptations to AT in response to exercise is essential to determine how AT contributes to the overall beneficial effect of exercise.

The beneficial effects of exercise on skeletal muscle and the cardiovascular system have long been known. Recent studies have focused on investigating the effects of exercise on adipose tissue and the effects that these exercise-induced adaptations have on overall metabolic health. Examination of exercise-induced adaptations in both white adipose tissue (WAT) and brown adipose tissue (BAT) has revealed marked differences in each tissue with exercise. In WAT, there are changes to both subcutaneous WAT (scWAT) and visceral WAT (vWAT), including decreased adipocyte size and lipid content, increased expression of metabolic genes, altered secretion of adipokines and increased mitochondrial activity. Adaptations specific to scWAT include lipidomic remodeling of phospholipids and, in rodents, the beiging of scWAT. The changes to BAT are less clear: studies evaluating the effect of exercise on the BAT of humans and rodents have revealed contradictory data, making this an important area of current investigation. In this Review, we discuss the exerciseinduced changes to WAT and BAT that have been reported by different studies and highlight the current questions in this field.

Summary Exercise improves whole-body metabolic health through adaptations to various tissues including adipose tissue, but the effects of exercise training on the lipidome of white (WAT) and brown (BAT) adipose tissue are unknown. Here, we utilized MS/MSALL shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT) and BAT. Three weeks of exercise-training decreased specific molecular species of phosphatidic acid (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS) in scWAT and increased specific molecular species of PC and PE in BAT. Exercise also decreased most triacylglycerols (TAGs) in scWAT and BAT. In summary, exercise-induced changes to the scWAT and BAT lipidome were highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflects selective remodeling in scWAT and BAT of both phospholipids and glycerol lipids in response to exercise training, thus providing a comprehensive resource for future studies of lipid metabolism pathways.