Background: Leptin is a new adipose-derived hormone discovered in 1994. It is vital in energy balance and weight regulation in humans. During pregnancy the placenta is an extra source of leptin. The role of leptin in pregnancy is not established. This has generated a lot of interest in leptin research in pregnancy. Leptin is being examined in pathological states that may have origin in adipose tissue and the placenta such as pre-eclampsia, intrauterine growth restriction and obesity. Aim and Method: This study measured concentrations of serum leptin in Black African women during late pregnancy in 68 women with pre-eclampsia, 92 healthy normotensive pregnant women and in 32 healthy non-pregnant women. In each group leptin levels were compared between obese (body mass index, BMI = or > than 30 kgm-2) and lean women. Serum leptin concentrations were measured by radioimmunoassay (RIA) technique. Results: Serum leptin levels were higher in pregnancy compared to non-pregnant women (26.66+/-16.13 ng/ml, 25.89+/-15.83 ng/ml vs 17.97+/-11.98 ng/ml, p=0.02). This is due to firstly, the extra fat accumulated as part of the maternal adaptation to pregnancy and secondlv, to the placenta-derived leptin. Other pregnancy hormones such as insulin, hcG, prolactin and oestrogen may modulate the serum levels of leptin in pregnancy. Simple anthropometric parameters (weight, BMI, circumferences of the mid upper arm (MAC), waist (WC), hip (HC), and thigh (TC) and waist-hip ratio (WHR)) were used to explore the relationship between leptin concentrations and obesity. All the parameters showed a positive correlation with serum leptin concentration in all the groups with the exception of WHR. Weight and BMI showed the greatest correlation both in pregnant (r=0.61 and r=0.58, respectively, p<0.001) and non-pregnant (r=0.74 and 0.79, respectively, p<0.001) women. However we did not find a significant difference in the concentrations of leptin between women with and those without pre-eclampsia (26.66 ng/ml vs 25.89 ng/ml, p=0.95). This probably means that adiposity is the predominant factor influencing levels of leptin in pregnancy. The other factors mentioned above play only a minor role. Indeed the mean serum leptin levels were higher in obese compared to lean women in both pregnant and non-pregnant women. Conclusion: Pregnancy is a hyperleptinaemic state. There is no difference in serum leptin levels between women with pre-eclampsia and healthy normotensive pregnant women. Serum leptin concentration is largely determined by the degree of adiposity both in and outside pregnancy. / Thesis (M.Med.)-University of Natal, Durban, 2001.

ATP-binding cassette transporters ABCA1 and ABCG1 initiate reverse cholesterol transport generating HDL particles, whereas ABCG5/G8 promote biliary cholesterol secretion thereby facilitating the last step of reverse cholesterol transport. Mutations in the leptin axis result in obesity and dyslipidemia in ob/ob and db/db mice. These mice have defective HDL clearance, increased plasma cholesterol and decreased biliary cholesterol elimination. My studies demonstrate that ABCG5/G8 protein is low in these animals and can be restored with caloric restriction or leptin replacement. To directly test whether ABCG5/G8 alone is able to correct reverse cholesterol transport defect, liver specific ABCG5/G8 expression was achieved in db/db mice by administration of adenoviral ABCG5 and ABCG8. Restoration of biliary cholesterol is able partially to correct dyslipidemia in obese mice, but only in the presence of ezetimibe, an inhibitor of cholesterol absorption. ABCG5/G8 is the body’s primary defense against toxic effects of plant sterols. Plant sterols are used as cholesterol lowering food supplements. However, increased plasma plant sterol concentrations are associated with vascular lesions in dyslipidemic patients and animals. My in vitro studies demonstrate that individual plant sterol alter ABCA1 and ABCG1 abundance, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells at levels found in humans that consume plant sterol supplements.

The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid beta (Aβ) peptide (a toxic peptide associated with neurologic disease) and attenuate hyperphosphorylation of the tau protein (another peptide prone to forming large insoluble structures causing neurodegeneration). From these studies we have elucidated that leptin resistant mice (which develop severe obesity and type-2 diabetes mellitus) with knock-in mutations for the amyloid precursor protein (APP) and presenilin-1 (PS1) genes develop extensive vascular pathology and cognitive impairments. Interestingly, these mice do not display increased levels of amyloid deposition in the brain. Additionally, increased tau phosphorylation occurs in these mice with leptin resistance. As a follow up to this study db mice were transduced, via adeno-associated virus, with the tau P301L mutant to induce the development of tangle pathology. These mice displayed no cognitive deficits, yet they displayed increases in both tau phosphorylation and tangle count within the hippocampus. Collectively, these studies indicate leptin resistance, obesity, and type-2 diabetes mellitus promote the development of cerebrovascular and neurofibrillary tangle pathologies associated with neurodegeneration and dementia. These observations open many previously unexplored avenues for developing novel therapeutics to treat these devastating diseases.

A major cause of morbidity and early death in the Western societies is cardiovascular disease (CVD) secondary to atherosclerotic disease. Metabolic aberrations have been linked to CVD. Particular combinations of these so-called risk markers are common and (central) obesity, Type 2 diabetes, impaired glucose tolerance, hypertension, dyslipidemia, dysfibrinolysis and hyperinsulinemia are often associated. This has been entitled the Insulin Resistance Syndrome (1RS), due to underlying insulin resistance. Moreover, aberrations in circulating levels of androgens and IGF-binding proteins are associated with 1RS. The main hypothesis in this thesis was that increased levels of leptin, the recently discovered adipocyte derived hormone in combination with obesity may be an important factor in the link between 1RS and the development of CVD. The association between leptin levels and variables associated with the Insulin Resistance Syndrome was studied in a healthy sample (n=163) of middle-aged men and women from the northern Sweden MONICA health survey. Central obesity was associated with high levels of leptin and insulin in men and women. In contrast, central obesity was linked to low testosterone levels in men, whereas in women, central obesity was associated with high testosterone but low SHBG levels. Furthermore, in males and postmenopausal women central obesity was a major determinant for circulating leptin. Leptin levels were associated with biochemical androgenicity in non-obese men and women. The direction of this association was dependent on gender and body fat distribution. Specifically, testosterone was inversely associated to leptin in non-obese men and in normal weight women whereas testosterone was positively associated to leptin in non-obese women. In contrast, adiposity and insulin levels, but not testosterone, were associated to leptin in obese men and women. Similarly, leptin was associated to IGFBP-1 and proinsulin in non-obese men and premenopausal women. Hyperleptinemia was significantly associated to high PAI-1 levels in men and in centrally obese women. In a multivariate model, high leptin levels predicted PAI-1 levels in men but not in women. Finally, leptin levels were related to blood pressure in obese men. The impact of hyperleptinemia on future risk for development of CVD was tested in a nested case-referent study based on the MONICA and the Västerbotten Intervention Program surveys. It was found that hyperleptinemia and high total cholesterol levels were associated with increased risk for development of myocardial infarction whereas high levels of apolipoprotein A-l were protective. Hyperleptinemia together with hypertension remained as significant risk markers for hemorrhagic stroke whereas hypertension alone predicted ischemic stroke. The combinations of hyperleptinemia on one hand and low apolipoprotein A- 1 and high blood pressure on the other were associated with a pronounced increased risk for myocardial infarction and hemorrhagic stroke, respectively. In conclusion, hyperleptinemia is independently associated with several risk markers for CVD included in the insulin resistance syndrome. Furthermore, high leptin levels predict the development of CVD. / <p>Härtill 5 uppsatser</p> / digitalisering@umu

Motivation: Abdominal obesity (hereafter referred to as "obesity") is becoming the biggest "global epidemic" of our modern times. It is associated with a range of diseases, including cardiovascular diseases and hypertension. Recent research showed that an increase in sympathetic activity is of central importance in the pathogenesis of obesity-related diseases. Increased leptin levels and impaired baroreflex sensitivity have both been independently associated with abdominal obesity and increased sympathetic activity. A perception of poorer health may also contribute to the physiological characteristics of obesity-related diseases. A lack of data regarding sympathetic activity, leptin levels, baroreflex sensitivity and perception of health in Africans, serves as a motivation for conducting this study. Objective: To investigate the contributions of leptin levels, baroreflex sensitivity and perception of health data to increased sympathetic activity in lean and obese African women from South Africa. Methodology: The manuscript presented in Chapter 2 made use of the data obtained in the POWIRS (Profiles of Obese Women with the Insulin Resistance Syndrome) study. A group of 102 urbanized African women, living in the North-West Province of South Africa, was recruited according to body mass indexes. Only 85 subjects were included for analysis due to incomplete datasets. For this study, subjects were divided into lean and obese groups according to their waist circumferences. Anthropometric measurements were done according to standardized methods. Resting cardiovascular measurements were obtained from Finometer observations. Resting, fasting levels of leptin were calculated after radioimmunoassay analyses. Subjective perception of health was determined by means of the 28-item General Health Questionnaire. Comparisons between the groups were done using analysis of covariance (ANCOVA) whilst adjusting for cardiovascular risk factors (age. smoking, alcohol consumption and physical activity). Correlation coefficients were determined to indicate any associations between leptin, baroreflex sensitivity and perception of health with sympathetic activity (represented by heart rate) and other cardiovascular variables. The study was approved by the Ethics committee of the North-West University and all the subjects gave informed consent in writing. The reader is referred to the Methods section in Chapter 2 for a more detailed description of the subjects, study design and analytical procedures used in this dissertation. Results and conclusion: Results from this study indicate that obese African women, compared to lean African women, were older, reported higher physical activity, and exhibited higher diastolic and mean blood pressure, heart rate, cardiac output, arterial compliance, leptin and hypertension prevalence rate values. In lean African women social dysfunction was positively associated with diastolic and mean blood pressure and arterial resistance, and negatively with arterial compliance. In obese African women baroreflex sensitivity was negatively associated with diastolic blood pressure, which could be an indication of impaired baroreflex sensitivity. In this obese group a perception of social dysfunction was associated with decreased heart rate. Although leptin and heart rate were significantly higher in the obese Africans, no significant correlations existed between these variables to reflect leptin's enhancement of sympathetic activity. However, leptin correlated weakly but positively with cardiac output (p = 0.054, r = 0.32). In conclusion, baroreflex sensitivity (although similar between groups) and leptin seem to contribute to blood pressure and thus hypertension in obese African women, possibly through increased sympathetic activity and volume loading. A perception of poorer health, especially a perception of social dysfunction, could possibly contribute to this image. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2007.

Forensiese assesseringstegnieke wat tydens ondersoeke na kinder seksuele misbruik benut word, het in n hoë mate mettertyd ontwikkel. Navorsing het n waardevolle bydrae gelewer tot effektiewe en geskikte assesseringstegnieke. Verdere navorsing is egter nodig om die bestaande tegnieke te ondersoek. Die persoon wat by forensiese assesserings betrokke is, kan baat vind by die leiding wat navorsing bied. Op grond hiervan het die navorser ondersoek ingestel na die forensiese assesseringstegnieke wat tans in die praktyk deur forensiese maatskaplike werkers benut word. Gedurende die ondersoek is verskeie tegnieke wat tydens forensiese assesseringsonderhoude benut word, geïdentifiseer en bespreek. Die sistematiese aanrakingseksplorasie is vir die doel van hierdie studie deur die navorser uitgesonder. Hierdie tegniek is aan die hand van n gevallestudie bestudeer en bespreek. Ondersoek is ook ingestel na die menings van maatskaplike werkers wat in die forensiese veld werksaam is, asook dié van justisie–amptenare, onder wie landdroste en staatsaanklaers, wat in die hof vir seksuele misdrywe werksaam is, ten opsigte van die benutting van die sistematiese aanrakingseksplorasie. Die justisie–amptenare was aanvanklik nie vertroud met die tegniek nie. Nadat literatuur vir bestudering aan hulle beskikbaar gestel is, is vasgestel dat hulle ontvanklik is vir en positief staan teenoor die benutting van die sistematiese aanrakingseksplorasie. Die ondersoek het ten doel gehad: * Om deur middel van n literatuurstudie die forensiese assesseringstegnieke wat tans in die praktyk benut word, te identifiseer en te bespreek; en * Om die sistematiese aanrakingseksplorasietegniek aan die hand van n literatuurstudie en empiriese navorsing te evalueer. Samevattend kan gestel word dat die tegnieke, soos in hierdie navorsing bespreek, deel behoort uit te maak van die protokol van die professionele persoon wat die seksueel misbruikte kind assesseer. Hierdie navorsing het bevind dat die sistematiese aanrakingseksplorasie n waardevolle forensiese assesseringstegniek is ten opsigte van die seksueel misbruikte kind. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Forensiese assesseringstegnieke wat tydens ondersoeke na kinder seksuele misbruik benut word, het in n hoë mate mettertyd ontwikkel. Navorsing het n waardevolle bydrae gelewer tot effektiewe en geskikte assesseringstegnieke. Verdere navorsing is egter nodig om die bestaande tegnieke te ondersoek. Die persoon wat by forensiese assesserings betrokke is, kan baat vind by die leiding wat navorsing bied. Op grond hiervan het die navorser ondersoek ingestel na die forensiese assesseringstegnieke wat tans in die praktyk deur forensiese maatskaplike werkers benut word. Gedurende die ondersoek is verskeie tegnieke wat tydens forensiese assesseringsonderhoude benut word, geïdentifiseer en bespreek. Die sistematiese aanrakingseksplorasie is vir die doel van hierdie studie deur die navorser uitgesonder. Hierdie tegniek is aan die hand van n gevallestudie bestudeer en bespreek. Ondersoek is ook ingestel na die menings van maatskaplike werkers wat in die forensiese veld werksaam is, asook dié van justisie–amptenare, onder wie landdroste en staatsaanklaers, wat in die hof vir seksuele misdrywe werksaam is, ten opsigte van die benutting van die sistematiese aanrakingseksplorasie. Die justisie–amptenare was aanvanklik nie vertroud met die tegniek nie. Nadat literatuur vir bestudering aan hulle beskikbaar gestel is, is vasgestel dat hulle ontvanklik is vir en positief staan teenoor die benutting van die sistematiese aanrakingseksplorasie. Die ondersoek het ten doel gehad: * Om deur middel van n literatuurstudie die forensiese assesseringstegnieke wat tans in die praktyk benut word, te identifiseer en te bespreek; en * Om die sistematiese aanrakingseksplorasietegniek aan die hand van n literatuurstudie en empiriese navorsing te evalueer. Samevattend kan gestel word dat die tegnieke, soos in hierdie navorsing bespreek, deel behoort uit te maak van die protokol van die professionele persoon wat die seksueel misbruikte kind assesseer. Hierdie navorsing het bevind dat die sistematiese aanrakingseksplorasie n waardevolle forensiese assesseringstegniek is ten opsigte van die seksueel misbruikte kind. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Darbo tikslas: Nustatyti nerujojančių ir neapsivaisinančių paršavedžių leptino geno (LEP) polimorfizmą ir leptino koncentraciją kraujyje bei įvertinti jų įtaką lytinį ciklą reguliuojantiems veiksniams. Darbo uždaviniai: 1. Nustatyti normalių (NP) ir nerujojančių bei neapsivaisinančių (NNP) paršavedžių leptino geno įvairovę. 2. Nustatyti leptino geno polimorfizmo (LEP) įtaką paršavedžių lašinių storiui po paršelių atjunkymo. 3. Įvertinti leptino geno polimorfizmo įtaką gimstančių paršelių gyvybingumui bei išsaugojimui. 4. Nustatyti leptino geno polimorfizmo įtaką paršavedžių brokavimo priežasčiai. 5. Nustatyti ir palyginti leptino koncentraciją skirtingų leptino genotipų paršavedžių kraujyje. 6. Įvertinti ir palyginti leptino geno polimorfizmo įtaką paršavedžių kraujo biocheminiams rodikliams. 7. Įvertinti dėl nerujojimo arba neapsivaisinimo išbrokuotų paršavedžių kiaušidžių funkcinę būklę atsižvelgiant į leptino geno polimorfizmą. 8. Nustatyti leptino geno polimorfizmo įtaką NNP paršavedžių gonadotropinių ir lytinių hormonų sekrecijai. 9. Nustatyti leptino geno polimorfizmo įtaką kiaušidžių morfologijai. 10. Nustatyti leptino koncentracijos kraujyje įtaką kiaušidžių morfologijai. Mokslinis darbo naujumas: Pirmą kartą buvo nustatytas leptino (LEP) geno polimorfizmas neapsivaisinančioms ir nerujojančioms (NNP) paršavedėms ir nustatyta šio geno įtaka šių paršavedžių reprodukcinių savybių sutrikimo pasireiškimui. Įvertinta leptino (LEP) geno polimorfizmo ir leptino koncentracijos... [toliau žr. visą tekstą] / The aim of the study: Define anoestrous repeat-breading sows’ leptin gene (LEP) polymorphism and leptin concentration in blood as well as evaluate its influence to the factors regulating oestrus cycle. Goalsof the study: 1. Define a diversity of leptin gene in normal sows (NS) and in anoestrous repeat-breading sows (NNS). 2. Define an influence of leptin gene (LEP) polymorphism to sows’ fat thickness after weaning. 3. Evaluate the influence of leptin gene polymorphism to newborn piglet viability and survival. 4. Define causal relationship of leptin gene polymorphism on sows culling rate. 5. Define and compare leptin concentration in blood of different leptin genotypes sows. 6. Evaluate and compare the influence of leptin gene polymorphism on sows’ blood biochemical parameters. 7. Evaluate the functional ovarian status of sows, culled due to anoestrous or failure to conceive, considering leptin gene polymorphism. 8. Define an influence of leptin gene polymorphism to secretion of NNS sows’ gonadotropin hormones and sex hormones. 9. Define an influence of leptin gene polymorphism on ovarian morphology. 10. Define an influence of leptin concentration in blood on ovarian morphology. Research novelty: For the first time leptin gene (LEP) polymorphism was determined for non-conceiving and anoestrous sows (NNS) as well as the influence of this gene on reproductive disorders in sows. We also assessed the effect of leptin gene (LEP) polymorphism and leptin concentration on NNS sows’... [to full text]

At the beginning of this project it was known that functional electrical stimulation (FES) rowing was technically feasible, but no studies on health benefits had been conducted and it was unclear what levels of fitness could be reliably attained by spinal cord injured (SCI) users. This thesis shows that training with the first-generation of the FES-rowing system (RowStim II), seven paraplegics achieved high V02peak values (21.0 - 27.9 ml-kg-1-min-1) and a significant (10%) increase in V02peak. This was also found to significantly improve insulin sensitivity and leptin levels but it had no significant effect on lipid profiles or body composition, possibly caused by technological limitations of the RowStim 11. However, training volumes were positively correlated with improvements in lipid profile and body composition. This motivated further technical development of the RowStim to enable paraplegics to train harder and longer. The development included a more stable seat configuration with redesigned trunk retaining straps, a rigid low friction carriage/brake system, improved leg stabiliser, improved stimulation control and a gravity-assisted return phase. This RowStim III has enabled paraplegics to participate in the British (2004, 2005 and 2006) and World Indoor Rowing Championships (2006). The rowers have achieved higher exercise intensities (26.8 -31.0 ml. kg- I .min-1) and increased exercise volumes (1,150 kcal-week-1) with the RowStim III. Such levels of physical activity, which are difficult to achieve for paraplegics using traditional exercises, are correlated with significant health benefits in the able-bodied. Preliminary results suggest that perfusion of the quadriceps muscle during FES-rowing might limit the exercise time in novice rowers. Other preliminary data from pressure mapping indicate that there is a dynamic pattern during FES-rowing, which might reduce the risk for pressure sores during FES-rowing. This thesis shows that FES-rowing is now a rapidly developing exercise modality, which has been shown to enable safe and well-tolerated exercise for individuals with SCI. It can offer unprecedented levels of cardiovascular fitness, competitive challenges and potentially important health benefits.

Central resistance to the actions of insulin and leptin is strongly associated with obesity and type 2 diabetes mellitus (T2DM). These anorexigenic hormones modulate one another’s actions at the neuronal level. To investigate the cellular events underlying the effect of insulin resistance on leptin modulation of hypothalamic neurons, a neuronal cell model was established. The rHypoE-19 cell line expresses the insulin and leptin receptors alongside a complement of signaling molecules rendering it an appropriate model to study the molecular events underlying leptin and insulin crosstalk. Hyperinsulinemia was used to induce insulin resistance and leptin regulation of the rHypoE-19 neurons was analyzed prior to and following the induction of insulin resistance. It was found that the attenuation of insulin signal transduction affects leptin signaling and transcriptional modulation of the rHypoE-19 neurons. These studies will ultimately lend itself to an improved understanding of the complex cellular events that accompany neuronal hormone resistance.