PubMed · 8155154
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L M Wilson. 1994-02-15. Abstinence or controlled drinking?. https://pubmed.ncbi.nlm.nih.gov/8155154/
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Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms. Here, we demonstrate that administration of an FGF21 analog to alcohol-preferring non-human primates reduces alcohol intake by 50%. Further, we reveal that FGF21 suppresses alcohol consumption through a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala. Our results illustrate how FGF21 suppresses alcohol consumption through a specific population of neurons in the brain and demonstrate its therapeutic potential in non-human primate models of excessive alcohol consumption.
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There are lingering questions regarding the relation between alcohol consumption and breast cancer risk in women. The authors performed a meta-analysis of epidemiologic studies carried out through 1999 to examine the dose-response relation and to assess whether effect estimates differed according to various study characteristics. Overall, there was a monotonic increase in the relative risk of breast cancer with alcohol consumption, but the magnitude of the effect was small; in comparison with nondrinkers, women averaging 12 g/day of alcohol consumption (approximately one typical drink) had a relative risk of 1.10 (95% confidence interval (CI): 1.06, 1.14). Estimates of relative risk were 7% greater in hospital-based case-control studies than in cohort studies or community-based case-control studies, 3% greater in studies published before 1990 than in studies published later, and 5% greater in studies conducted outside of the United States than in US studies. The findings of five US cohort studies published since 1990 yielded a relative risk of 1.06 (95% CI: 1.00, 1.11) for consumers of 12 g/day, as compared with nondrinkers. Cohort studies with less than 10 years of follow-up gave estimates 11% higher than cohort studies with longer follow-up periods. No meaningful difference was seen by menopausal status or type of beverage consumed.