Macrohih2a1 Case Study

Genetic research of obesity was partly successful in establishing obesity in model organisms – rodents where obesity occurs spontaneously together with other pathological aspects (insulin resistance, …). The main cause of monogenic obesity in these model organisms are common mutations always present in only one gene. Results of research on model organisms allowed us to understand biological mechanisms of calorie intake and regulation and maintenance of body weight. The most important insight into obesity was achieved in 1994 after discovery of ob gene encoding for leptin. In two years period, using screening method, candidate homologous genes, selected on genetic study basis on mice, another five genes were identified. Mutations on these genes were found to be the cause of autosomal recessive or dominant monogenic obesity. Products of these genes are leptin and its receptor, proopiomelanocortin (POMC) melanocortin receptor 4 (MC4R) and

Although scientists have identified genes as being one of the factors contributing to obesity, knowing what specific genes involved would be helpful. The Friedman group decided to try and find those specific genes with a series of breeding experiments of mice. The genes were mapped out and the group found a 650-kilobase segment on mouse chromosome 6 to be responsible and named it the ob gene (for obese)(Marx). This means scientists have found a gene responsible for the obese mice which became an important step in finding treatment options for what is now looking like a complicated issue. The next question to answer was whether this gene was being produced in adipose (fat) tissue. This would help determine if the gene was responsible for creating the unneeded fat. The search paid off as one gene was found being

A person’s genetic make up has a significant influence on whether the person will become obese or not. If both parents are obese, the likelihood that their children may end up being obese too is higher compared to a situation where neither of the parents is obese or where only one of the parents is obese. This is particularly so because genetics influence the way the body stores energy and how energy is used. This can be seen in the differences that have recorded in the basal metabolic rates (BMR) among groups of people who differ by age, gender and the make up of their bodies. People who have a low metabolic rate have a higher risk of becoming overweight. The genetic similarities shared by members of one family can explain why people who come form certain families end up being overweight (DeBruyne, Pinna

Although the mechanism of obesity development is not fully understood, it is confirmed that obesity occurs when energy intake exceeds energy expenditure. There are multiple etiologies for this imbalance, hence, and the rising prevalence of obesity cannot be addressed by a single etiology (Dehghan et al., 2005, p.

Exercise 4: Endocrine System Physiology: Activity 1: Metabolism and Thyroid Hormone Lab Report Pre-lab Quiz Results You scored 100% by answering 6 out of 6 questions correctly. 1. Which of the following statements about metabolism is false? You correctly answered: d. All of the energy from metabolism is ultimately stored in the chemical bonds of ATP. 2. Thyroxine is You correctly answered: c. the most important hormone for maintaining the metabolic rate and body temperature. 3. Thyroid-stimulating hormone (TSH) is You correctly answered: b. produced in the pituitary gland. 4. An injection of TSH to an otherwise normal animal will cause which of the following? You correctly answered: d. goiter development 5. Thyrotropin-releasing hormone

On a molecular level, fat tissue is normally the largest organ in humans and is involved in mechanisms and pathways that deal with longevity. Fat tissue is not only involved in energy storage but is also important in immune and endocrine function, thermoregulation, mechanical protection, and tissue regeneration (Tchkonia et al., 2010). Adipose tissue is able to protect against infection and trauma. It is also able to produce and activate hormones, including IL-6, IGF-1, and glucocorticoids, as well as prevent heat loss (Tchkonia et al., 2010). Throughout life, changes in fat distribution and function is constantly occurring and in older individuals, these changes correspond to a number of health disorders like hypertension, cancers, cognitive dysfunction, and diseases like diabetes, heart attacks, and strokes, as previously noted (Tchkonia et al., 2010). As people age, their body composition increases in fat mass and decreases in muscle mass, regardless of their body weight or BMI (Dorner and Rieder, 2011).

Some obese and overweight individuals have single mutations in their genes, although this is uncommon in the population. Most obese individuals have mutations on multiple chromosomes, which interact with one another. Of the few reported cases of monogenic obesity, the primary cause was a mutation in the melanocortin 4 receptor gene. These mutations account for 6-8% of severe inheritable obese symptoms, with the common variant of the MC4R gene being carried by 22% of the general population. With a loss of function in the gene, it has led to an increased appetite in childhood. Treatment for MC4R deficiency or other mutations has not be done yet, due to the low prevalence of variants in the general population. There is a need for future research to identify which specific genes or groups of genes have a link to obesity. It is recommended the testing will have practical implications for the mechanism-based therapy as well as effective and specific protocols. This should be the case for individuals who have the muted mutation and the protocols should be based on lifestyle intervention and pharmacological or surgical

Insulin resistance can also be caused by increased triglycerides and free fatty acids intake. This is due to the effect Triglycerides and free fatty acids have on insulin stimulated signal pathways, translocation protein-4 and glucose uptake (Choi, Jung, Park, & Song, 2004). It is found that CLA has a regulatory effect on glucose and lipid metabolism regulators. CLA affects the PPAR-y ligand, a major receptor that influences the expression and transcription of genes that are related to the metabolic effects of glucose and lipids. Such protein regulators as aP2, insulin-dependent glucose transporter 4, FATp, ACS and adiponectin are all influenced by increased CLA. (Xiao-Rong Zhoua, Chang-Hao Suna, Jia-Ren Liua, b, Dan Zhaoa, 2008). It was also theorized that CLA may act on other glucose regulators such as phosphoenolpyruvate carboxylase, glucose-6-phosphate, glucokinase, sterol-regulation element finding protein, acyl coenzyme A oxidase, fatty acid synthase and uncoupling protein. Testing done on rats with a mixture of cis 9, trans 11 and trans 10, cis 12 CLA had found that the only effected regulatory agents were regulators involved in gluconeogenesis such as Phosphoenol carboxykinase and transcriptional factors, sterol-regulating element binding protein-1c and PPAR-y (Choi, Jung, Park, & Song, 2004). The main regulatory effect on insulin resistance was the effect on ligand PPAR-y, a key regulator in lipid homeostasis. Mixtures of CLA isomers consisting of cis 9, trans 11 and trans 10,cis 12 effect gene expression of PPARy mRNA in rats. It was found to have affected the levels of aP2, FATP, ACS and adipoenectin mRNA expression in adipose tissue. CLA increased These regulatory proteins resulting in an uptake of free fatty acids into the adipose tissue and decreasing uptake into the muscle tissue. This has been found to improve muscle insulin

Obesity has reached epidemic proportions in the United States and developing countries. Although the trend of decreased physical activity and increased caloric intake is probably responsible for the recent rise in obesity, it is important to understand that these trends are playing out on a background of genetic variation in the population. Each individual's genetic background remains an important determinant of susceptibility to obesity. Discovery of the genes involved in the development of common forms of obesity, thereby identifying pathways that are causal in patients, will guide clinicians and scientists in designing more effective therapies and in identifying high-risk individuals for early intervention.

Obesity today is a major health issue in populations across the globe. The lifestyle changes occurring in the 21st  century have resulted in ‘abundance’ of all things – including that of visceral fat in all age‐groups across the globe.  There are many health‐conditions already linked with obesity – such as diabetes, high‐blood‐pressure, congestive  heart‐failure, reproductive complications, etc – but, could being obese make one susceptible to cancer? Or possibly  make for a worse cancer prognosis?  These issues are addressed in this report, with references to many studies performed at the population level, and at  the molecular level –

Type 2 diabetes results from a multitude of defects: impaired insulin secretion, insulin resistance, and defects in GLP-1 secretion and action. Prior to the onset and throughout the course of the disease, beta cell function and pancreatic mass deteriorate; causes may be lipotoxicity, glucose toxicity, increased age, genetics, insulin resistance, and incretin deficiency. Insulin resistance takes place in the liver, adipose, and skeletal tissues (1), ultimately leading to decreased peripheral uptake and hyperglycemia. In the liver, lack of insulin action results in gluconeogenesis and glycogenolysis, further potentiating the hyperglycemia. In fat cells, decreased GLUT4 leads to excessive release of free fatty acids and adipocytokines (2). Because

Obesity is a disorder of the Endocrine System. Obesity means having too much body fat, it occurs over time when more calories are eaten than being use. The balance between calories-in and calories-out differs for each person. Factors that might affect weight consist of your genetic makeup, overeating, eating high-fat foods, and not being physically active. Furthermore, several endocrine abnormalities are reported in obesity. Some of these abnormalities are considered as contributory factors for the development of obesity, whereas others are considered to be secondary effects of obesity and usually are restored after weight loss. Thyroid hormones usually are normal in obesity, with the exception of T3 which is elevated. Prolactin is normal but prolactin response to different stimuli is dulled. GH is low and GH response to stimuli is dulled. IGF-I levels are normal or elevated. Cortisol, ACTH, and urine free cortisol levels are usually normal; however, a hyperresponsiveness of the HPA axis with increased cortisol and ACTH response to stimulatory tests is observed in extremely obese individuals.

Both animal and clinical studies have demonstrated that obesity leads to ovarian dysfunction through oxidative and ER stress and inflammation (26,65,66,74-78). Obesity leads to excess lipids, glucose, insulin, and leptin in variety of ovarian cells including: granulosa cells, cumulus cells, oocytes, and early embryos (ref more;(65,79,80)). Because leptin contributes to follicular growth, steroidogenesis, oocyte maturation and embryo development, hyperleptinemia seen in obese women may disrupt these processes (30,58,70,75,78,81-96). Similarly, insulin resistance and or hyperinsulinemia, have been shown to alter ovarian morphology, ovarian insulin signaling, ovulation and maturation of oocytes (23,30,36,39,40,71,73,74,97-107). Obesity leads to elevated levels of circulating lipids as well as lipid accumulation in the ovary which are associated with decreased granulosa cell numbers, increased apoptosis, greater lipid accumulation in cumulus cells, decreased oocyte nuclear maturation, and changes in substrate metabolism and proliferation in embryos (18,36,55,63,65,67,75,79,90,92,108-112). Greater oxidative stress and chronic low grade inflammation, as seen in obese animals and humans, have also been shown to alter oocyte maturation and fertilization, embryo development and pregnancy success (19,26,65,66,68,69,74,77,78,104,105,109,110,113-120). Lastly, obesity leads to a variety of oocyte mitochondrial defects, including

Experimental approach: Mice metabolic rates, food intake, energy expenditure, locomotor activity, and respiratory quotients will be measured using the comprehensive laboratory animal monitoring system (CLAMS) chambers (Columbus Instruments, OH, USA) in collaboration with Dr. Nathan LeBrasseur as previously described [12]. We will also assess insulin resistance by measuring the homeostasis model assessment of insulin resistance (HOMA-IR) [13] and performing glucose tolerance test on the mice. We will employ micro-CT to assess the relative contribution of visceral versus subcutaneous fat in body adiposity in the mice from the different experimental groups.

A research was carried out by an International research partnership with over two hundred researchers to identify the genetic causes of overweight and obesity. The research was carried out on over 260000 people. There are over 50 loci in the human genome that affect the dangers of overweight. They found seven new other sites on the man’s genome where small differences in the genes affect the dangers of obesity and overweight. During