Sara Holmberg

Origins of the many NPY-family receptors in mammals

The NPY system has a multitude of effects and is particularly well known for its role in appetite regulation. We have found that the five presently known receptors in mammals arose very early in vertebrate evolution before the appearance of jawed vertebrates 400 million years ago. The genes Y(1), Y(2) and Y(5) arose by local duplications and are still present on the same chromosome in human and pig. Duplications of this chromosome led to the Y(1)-like genes Y(4) and y(6). We find evidence for two occasions where receptor subtypes probably arose before peptide genes were duplicated. These observations pertain to the discussion whether ligands or receptors tend to appear first in evolution. The roles of Y(1) and Y(5) in feeding may differ between species demonstrating the importance of performing functional studies in additional mammals to mouse and rat.

Knee osteoarthritis and body mass index: a population-based case-control study.

Objective: It is well established that overweight is related to osteoarthritis of the knees. The aim of this study was to investigate the risk of knee osteoarthritis for men and women in relation to body mass index (BMI) within the normal weight range and to assess the effect of former versus current weight. Methods: A population‐based case–control study was carried out in the southern part of Sweden, including 825 cases with X‐ray verified femorotibial osteoarthritis and 825 age‐, sex‐, and county‐matched population controls. Mailed questionnaire data on weight, height, and confounding factors (heredity, smoking, knee injuries, and physical activity) were collected and analysed using logistic regression models. The response frequency was 89%. Results: Mean age of the participants was 63 years, and 57% were women. The adjusted risk of knee osteoarthritis was increased fourfold in men with a current BMI 23 to <25 kg/m2 as compared to men with BMI <23 kg/m2 (OR 4.0, 95% CI 1.7–9.5). The commensurate risk for women was 1.6 (95% CI 0.9–3.1). BMI at 30 years of age was similarly related to knee osteoarthritis. Conclusion: A moderate increase in BMI, within the normal weight range, was significantly related to knee osteoarthritis among men. Overweight at any time was related to knee osteoarthritis.

Musculoskeletal symptoms among farmers and non-farmers : A population-based study

Abstract Farming has been considered a high-risk occupation for musculoskeletal disorders. However, documentation of the increased risk is weak except for hip osteoarthritis. 1,013 full-time farmers in nine Swedish municipalities and 769 non-farmers (referents), matched for age, sex, and residential area, participated in the study. Information about medical history, consultations, and sick leave for musculoskeletal disorders was obtained by questionnaire and interview. The farmers reported significantly more symptoms affecting the hands and forearms, low back, and hips than did the non-farmers, and a non-significant trend in the same direction was found for symptoms from the neck, shoulders, and knees. However, the farmers did not seek medical advice more often than the referents, and they reported significantly less sick leave for these problems. Thus, farmers appear to have more musculoskeletal symptoms than do non-farmers

Knee injuries account for the sports-related increased risk of knee osteoarthritis.

Increased risk of osteoarthritis has been found among athletes active in different kinds of sports. Knee injury is an established risk factor for knee osteoarthritis. In this population‐based case–control study we investigated the risk of knee osteoarthritis with respect to sports activity and previous knee injuries. A total of 825 cases with x‐ray‐verified femorotibial osteoarthritis were identified at six hospitals in southern Sweden. The cases were matched (age, sex and residential area) with 825 controls from the general population. Mailed questionnaire data on sports activity for more than 1 year after the age of 16, knee injuries and confounding variables (weight, height, heredity, smoking and occupation) were collected and analyzed using logistic regression models. The response frequency was 89%. Among men knee osteoarthritis was related to soccer (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1–2.2), ice hockey (OR 1.9, 95% CI 1.2–3.0) and tennis (OR 2.0, 95% CI 1.1–3.8) but not to track and field sports, cross‐country skiing, and orienteering. After adjustment for confounding variables soccer and ice hockey remained significantly related to knee osteoarthritis, but after adjustment for knee injuries no significant relation remained. The sports‐related increased risk for knee osteoarthritis was explained by knee injuries.

Relationship of Sense of Coherence to Other Psychosocial Indices

Summary: The concept of “sense of coherence” (SOC) has been widely recognized since it was first introduced by Antonovsky. The originality and usefulness of the SOC scale and its relation to other psychosocial measures has been the subject of lively debate. The aim of this paper was to test for associations between SOC and work-related psychosocial factors (mainly the Job Demand-Control model), general living conditions, education, and social network factors. Cross-sectional data from a population-based sample of 1782 rural males from nine counties in Sweden were analyzed with a multiple regression technique. The subjects were occupationally active at inclusion and the mean age was 50 years (range 40-60). SOC was assessed with the original 29-item questionnaire. Psychosocial variables and lifestyle factors were assessed using questionnaires and structured interviews. The mean SOC among the subjects was 152.3 (standard deviation, 19.4). A strong negative correlation was found between SOC and job demand, wh...

Chicken neuropeptide Y receptor Y2: structural and pharmacological differences to mammalian Y21

Here we report the molecular cloning of the chicken (Gallus gallus) neuropeptide Y (NPY) receptor Y2, the first non‐mammalian Y2 receptor. It displays 75–80% identity to mammalian Y2 and has a surprisingly divergent cytoplasmic tail. Expression of the receptor protein in a cell line showed that the receptor did not bind the mammalian Y2 selective antagonist BIIE0246. Furthermore, porcine [Leu31, Pro34]NPY, which binds poorly to mammalian Y2, exhibited an unexpectedly high affinity for chicken Y2. In situ hybridisation revealed expression in the hippocampus. Thus, the chicken Y2 receptor exhibits substantial differences with regard to sequence and pharmacological profile in comparison to mammalian Y2 receptors, while the expression pattern in the central nervous system resembles that observed in mammals.

The cloned guinea pig pancreatic polypeptide receptor Y4 resembles more the human Y4 than does the rat Y4

Pancreatic polypeptide (PP) is involved in gastrointestinal functions and forms, together with neuropeptide Y (NPY) and peptide YY (PYY), the PP-fold family of peptides. The PP-binding receptor subtype Y4 has so far been cloned in human, rat, and mouse, and displays extensive species differences regarding sequence, pharmacology, and distribution. To explore this variability further, we have cloned the Y4 receptor in the guinea pig, which is evolutionarily equally distantly related to both humans and rodents. The guinea pig Y4 receptor is 84% identical to the human Y4 receptor, but only 74-75% identical to the rat and mouse receptors. The two latter are 75-76% identical to human Y4. The guinea pig Y4 receptor bound 125I-hPP with a dissociation constant (Kd) of 29+/-3 pM. The pharmacological profile of guinea pig Y4 has the following rank order of potencies: PP > NPY approximately = PYY approximately = LP-NPY approximately = LP-PYY > NPY2-36 >> [D-Trp32]NPY. Thus, the guinea pig receptor is more similar to the human Y4 than to the rat Y4 both in sequence and pharmacology. This agrees with the greater identity between guinea pig and human PP compared to rat PP. These comparisons suggest that the rodent PPs and Y4 receptors have an accelerated replacement rate.

Pharmacological characterization of cloned chicken neuropeptide Y receptors Y1 and Y5

The neuropeptide Y (NPY) receptor subtypes Y1 and Y5 are involved in the regulation of feeding and several other physiological functions in mammals. To increase our understanding of the origin and mechanisms of the complex NPY system, we report here the cloning and pharmacological characterization of receptors Y1 and Y5 in the first non‐mammal, chicken (Gallus gallus). The receptors display 80–83% and 64–72% amino acid sequence identity, respectively, with their mammalian orthologues. The three endogenous ligands NPY, peptide YY (PYY) and pancreatic polypeptide (PP) have similar affinities as in mammals, i.e. NPY and PYY have subnanomolar affinity for both receptors whereas chicken PP bound with nanomolar affinity to Y5 but not to Y1. A notable difference to mammalian receptor subtypes is that the Y1 antagonist SR120819A does not bind chicken Y1, whereas BIBP3226 does. The Y5 antagonist CGP71863A binds to the chicken Y5 receptor. Anatomically, both Y1 and Y5 have high mRNA expression levels in the infundibular nucleus which is the homologous structure of the hypothalamic arcuate nucleus in mammals. These results suggest that some of the selective Y1 and Y5 antagonists developed in mammals can be used to study appetite regulation in chicken.

A prospective study of morbidity and mortality rates among farmers and rural and urban nonfarmers

Farmers are known to have lower morbidity and mortality rates than the mean for other occupational groups in the general population. Whether this is due to the urban-rural health gradient or to occupational factors related to farming is not clear. To explore this issue, we conducted a prospective study of farmers and matched rural and urban referents. Official hospital admission and mortality data for the years 1989-1996 were obtained. The relative risk of being admitted to hospital were 10% higher among rural and urban referents than among the farmers. The biggest differences were seen for mental and cardiovascular disorders. The odds of dying during follow-up did not differ between the two rural groups but were doubled among urban referents. In conclusion, the lower morbidity and mortality rates among farmers are partly due to the urban-rural health gradient but in addition salutogenic factors linked to farming seem to be active.

High dairy fat intake related to less central obesity: a male cohort study with 12 years' follow-up.

Abstract Objective. To study associations between dairy fat intake and development of central obesity. Design. A prospective population-based cohort study with two surveys 12 years apart. Setting. Nine municipalities selected from different parts of Sweden representing the rural areas in the country. Subjects. 1782 men (farmers and non-farmers) aged 40–60 years at baseline participated in a baseline survey (participation rate 76%) and 1589 men participated at the follow-up. 116 men with central obesity at baseline were excluded from the analyses. Main outcome measures. Central obesity at follow-up defined as waist hip ratio ≥ 1. Results. 197 men (15%) developed central obesity during follow-up. A low intake of dairy fat at baseline (no butter and low fat milk and seldom/never whipping cream) was associated with a higher risk of developing central obesity (OR 1.53, 95% CI 1.05–2.24) and a high intake of dairy fat (butter as spread and high fat milk and whipping cream) was associated with a lower risk of central obesity (OR 0.52, 95% CI 0.33–0.83) as compared with medium intake (all other combinations of spread, milk, and cream) after adjustment for intake of fruit and vegetables, smoking, alcohol consumption, physical activity, age, education, and profession. The associations between dairy fat intake and central obesity were consistent across body mass index categories at baseline. Conclusion. A high intake of dairy fat was associated with a lower risk of central obesity and a low dairy fat intake was associated with a higher risk of central obesity.