The Ghrelin Signalling System Is Involved in the Consumption of Sweets

The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose- intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours

Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease

Peer reviewe

Coffee and gene interaction. The effect on methionine and lipid metabolism

Background: Different dietary factors influence the risk of coronary heart disease (CHD), most likely in an interaction with genetic polymorphisms. The knowledge about such interactions is insufficient. Some observational studies have shown an association between coffee and CHD, others have not. Coffee consumption affects some CHD risk factors, e.g. plasma total homocysteine (tHcy) and serum total cholesterol. tHcy is negatively associated with folic acid, pyridoxine (vitamin B6) and vitamin B12, and is also influenced by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Serum cholesterol is affected by the APOE 2/ 3/ 4 polymorphism.Aims: To investigate if a supplement of 200 µg folic acid or 40 mg pyridoxine would decrease or eliminate the tHcy enhancing effect of coffee, and if the effect was dependent of the MTHFR C677T polymorphism. The study also gave the opportunity to study the serum cholesterol raising effect of filtered coffee and if the effect was influenced by APOE 2/ 3/ 4 polymorphisms.Method: The participants were 121 healthy non-smoking men (22%) and women (78%), 29-65 years old, not on blood lipid lowering drugs or vitamin B supplementation. The effect of coffee was studied in a prospective, controlled, double blind trial with four consecutive periods: 1. three weeks of coffee abstention (wash-out) 2. 4 cups (600 mL) coffee/day and 200 g folic acid/day or placebo for 4 weeks3. three weeks of coffee abstention (wash-out) 4. 4 cups (600 mL) coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks.Results: Three weeks of coffee abstention resulted in a tHcy decrease of 1.04 mol/L for the whole group (95% CI -1.45, -0.62). During the subsequent coffee consumption period there was a further decrease of 0.17 mol/L in the folic acid group. In the placebo group there was a tHcy increase of 1.26 mol/L, the difference was 1.43 mol/L (95% CI 0.80, 2.07). Pyridoxine supplementation had no significant effect on the tHcy level.The homocysteine increasing effect of coffee was mainly seen in individuals homozygous for the MTHFR 677T genotype. Folic acid supplement reduced the tHcy increase in these individuals. The two coffee abstention periods resulted in a significant serum cholesterol decrease of 0.22 mmol/L and 0.36 mmol/L, respectively. Consumption of 4 cups filter brewed coffee/day resulted in a significant serum cholesterol increase of 0.25 mmol/L and 0.15 mmol/L, respectively. APOE e2 positive individuals had lower serum cholesterol at baseline than APOE e2 negative individuals, but the APOE polymorphism had no influence on the serum cholesterol increasing effect of coffee.Discussion: The results are consistent with earlier intervention studies on the association between coffee and tHcy. Individuals with hyperhomocysteinemia, often homozygous for the MTHFR 677T allele, should have an adequate intake of folic acid to limit the homocysteine raising effect of coffee. The magnitude of the serum cholesterol enhancing effect of filter-brewed coffee was surprising, and has been shown in only two earlier intervention studies. Individuals with high serum cholesterol should limit their coffee consumption regardless of their APOE genotype

Relative validity of a short 15-item food frequency questionnaire measuring dietary quality, by the diet history method

Food frequency questionnaires (FFQ) are commonly used dietary assessment tools. The aim was to assess the relative validity of a 15-item FFQ, designed for the screening of poor dietary patterns with a validated diet history (DH). The study population was derived from the Gothenburg H70 Birth Cohort Studies. The DH registrations were harmonized in accordance with the FFQ frequencies. The agreement was assessed by Cohen’s kappa with corresponding confidence intervals (CI) for the frequency and categorical variables. Bland–Altman plots were used for the numeric variables. The study comprised data from 848 individuals (55.2% women). Overall, there was high agreement between the methods, with the exact and adjacent level of agreement over 80% for eight variables. The proportion attributed to the opposite frequency was fairly low for most of the frequency variables. Most of the kappa values were in fair or moderate agreement. The highest kappa values were calculated for the type of cooking fat (k = 0.68, CI = 0.63–0.72) and sandwich spread (k = 0.55, CI = 0.49–0.53), and the lowest for type of bread (0.13, CI = 0.07–0.20) and sweets (0.22 CI = 0.18–0.27). In conclusion, the FFQ showed overall good agreement compared with the DH. We, therefore, think it, with some improvements, could serve as a simple screening tool for poor dietary patterns. (This article belongs to the Special Issue Health Promotion in a Life Span Perspective)</p

Comparison of Apolipoprotein (apoB/apoA-I) and Lipoprotein (Total Cholesterol/HDL) Ratio Determinants. Focus on Obesity, Diet and Alcohol Intake

<div><p>The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.</p> </div

Association of total alcohol intake (alone, in a first model) and ethanol from difference sources (simultaneously included in a second model) with percent (%) difference in both the apolipoprotein (apoB/apoA-I) and the lipoprotein (total cholesterol/HDL) ratio (included on a logarithmic scale), from a multiple linear regression model adjusted for age, obesity, physical activity, smoking status, education, marital status, saturated fat intake, sucrose intake, the Recommended Food Score, gender (in combined analyses) and menopausal status plus estrogen use (in women).

<p>All ethanol and alcohol beverage variables were included as continuous variables in the models, divided by 10 in order to get an estimation of the effect on a scale of 10 g/day.</p>*<p>p<0.05,</p>**<p>p<0.01,</p>***<p>p<0.001.</p