Palatable food, clock genes and the reward circuitry

This thesis studied the interaction between diet-induced obesity and the 24h variations in behavior and physiology paced by the circadian system. Mice and rats were fed with a free choice high-fat high-sugar diet (fcHFHS). In mice, fcHFHS diet changed day-night eating patterns and PER2 clock-protein expression in the Lateral Habenula (LHb), a food-reward related area. In rats, no feeding patterns or clock-gene changes in LHb were found, however, Per2 gene expression was disrupted in the Nucleus Accumbens, which is indirectly connected to LHb. When blocking pharmacologically the glutamatergic functioning of the LHb, food intake was altered in both chow and fcHFHS-fed rats in a time-dependent manner. Finally, we tested the influence of Npas2 clock-gene on the disruption of rhythmic behavior produced by the fcHFHS-diet using Npas2 mutant and WT mice. Both genotypes, however, displayed similar altered eating patterns caused by the fcHFHS diet. Our findings indicate a relationship between nutrient type and an abnormal clock-gene expression in food reward-related areas, and an important role for the LHb in feeding behavior

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden