Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, lipid age was determined by measuring nuclear bomb test-derived 14C in adipocyte lipids. We report that during the average ten year life span of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate from fat tissue is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidemia, familial combined hyperlipidemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal play different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

Continuous turnover of neurons in the olfactory bulb is implicated in several key aspects of olfaction. There is a dramatic decline postnatally in the number of migratory neuroblasts en route to the olfactory bulb in humans, and it has been unclear to what extent the small number of neuroblasts at later stages contributes new neurons to the olfactory bulb. We have assessed the age of olfactory bulb neurons in humans by measuring the levels of nuclear bomb test-derived (14)C in genomic DNA. We report that (14)C concentrations correspond to the atmospheric levels at the time of birth of the individuals, establishing that there is very limited, if any, postnatal neurogenesis in the human olfactory bulb. This identifies a fundamental difference in the plasticity of the human brain compared to other mammals.

Systematic investigations and experience from several application projects on small carbon samples over a number of years have resulted in measuring the radiocarbon content of 10 μg C samples with an overall precision of typically 1%. A substantial reduction of the carbon contamination during graphitization was achieved, resulting in 31±30 ng modern and <100 ng 14C-free carbon. Thus, graphitization is no longer the limiting factor because earlier sample preparation steps usually introduce much larger contamination. The method has been extended to a variety of materials and applied to various projects. Realistic conditions for procedure development can only be achieved in the context of applications on true samples; methods developed are the lyophilization of samples in solution, combustion, ultraviolet oxidation, or carbonate hydrolysis with phosphoric acid, which allows to prepare samples for a wide range of applications. Insights gained from systematic investigations and from real applications are presented.

Despite known limitations of post treatment PET/CT imaging, this work indicates its potential for assessing inter-fractional changes and points to future developments for improved PET-based treatment verification.