OBESITY – how? and why?

1. OBESITY –how? and why? (C) 2011 Nutrition 3. Prepared by Leah Marmulla for use by Academy of Complementary Health. Use without written permission prohibited

2. WHAT IS OBESITY? HOW DOES IT HAPPEN? (Biesalki,H & Grimm,P. 2004, Pocket Atlas of Nutrition, Thieme) • Fat accumulation in tissues beyond normal levels is called obesity or adiposity. • The stages involved in the development of obesity are: • Adipocyte volume increases. • If caloric intake continues to exceed the requirements, preadipocytes may be transformed into additional adipocytes. • Since the triglycerides deposited in these adipocytes undergo constant metabolic transformation, an increase in the levels of all components of lipid metabolism ensues.

3. The cause of obesity is generally a sustained or repeated positive energy balance. That is excessive energy intake > energy requirements. • Both sides of this equation are influenced by exogenous factors: • Intake is influenced by taste, upbringing, environment during meals, psychological factors, portion size and such. • Requirements depend on physical activity at work and during leisure, gender, age disease states, nutritional status

4. Both sides are also subject to heredity components that have been shown to affect: • Feeding behaviour • Hunger and satiation • Efficiency of cellular energy production • Visceral fatty tissues have the highest metabolic rate. Therefore the android form (apple shape) of obesity tends to have more severe health consequences.

5. For purposes of evaluating obesity BMI tables are usually used since they correlate with body fat content. • Revise the concepts of: • Body Mass Index (BMI) Ht/wt ratio • Basal Metabolic Rate (BMR) - energy required to maintain energy for rest based on age, height and gender • Total Energy expenditure (TEE) – the amount of energy required to maintain BMR x activity level &/or injury factor

6. Calculate the Body Mass Index (BMI) for the following based on the information provided. Indicate the classification of the BMI calculated (e.g. underweight, normal, overweight, obesity, extreme obesity). • Gender: female Weight = 95 kg Height = 160 cm • Gender: male Weight = 82kg Height = 1.8 m • WHAT DO YOU SEE AS THE LIMITATIONS OF THIS TYPE OF MEASUREMENT?

7. EPIDEMIOLOGY • The following epidemiological information has been sourced from a report by the Australian Institute of Health and Welfare at: www.aihw.gov.au • In the 2003 Sentinel Site for Obesity Prevention in Victoria study, 7.9% of children aged 7–11 years were obese, and 26.7% were overweight • In a survey of NSW primary school children aged 7–11 years in 2000, the prevalence of obesity was 9.9% in boys and 7.1% in girls. The prevalence of overweight was as high as 26.2% in boys and 28.4% in girls.

8. Research from South Australia’s Child and Youth Help showed that the percentage of obese preschoolers rose from 3.5% for girls and 3.2% for boys in 1995 to 5.8% for girls and 4.1% for boys in 2002.

10. The most recent national data based on self-reported height and weight, the 2001 National Health Survey (NHS), showed 2.4 million Australian adults were estimated to be obese - 16% of men and 17% of women aged 18 years and over, had a BMI of 30 or more (Australia’s Health 2004). • Obesity could be a legacy of 1990s. The Australian Institute of Health and Welfare says that the prevalence of obesity rose alarmingly in the 1990’s – by 71% for men, and 80% for women. • It is estimated that in Australia, 20-25% of children and adolescents are overweight or obese. The equals a total of one million overweight or obese children and adolescents. • The World Health Organisation has declared obesity a “global epidemic” (Australia’s Health 2004) • A further 4.9 million Australian adults were estimated to be overweight but not obese (42% of men and 25% of women aged 18 years and over, with a BMI of 25 or more but less than 30) (Australia’s Health 2004).

11. Childhood Obesity Trend 1995 - 2008 http://www.abs.gov.au/AUSSTATS/abs@.nsf/Lookup/4102.0Main+Features20Sep+2009

12. BMI Changes 1989-2005 Women Men

13. WHAT DOES ALL OF THIS MEAN FOR US AS CAM PRACTITIONERS?

14. OBESITY IS A KILLER • In 2002, malignant neoplasm's, ischaemic heart diseases and cerebrovascular diseases were the leading underlying causes of death responsible for 57% of all deaths. Obesity contributes significantly to these deaths. (Eddy,S. 2005, Food as Medicine presentation, Health Schools Australia) • Australian figures for obesity related illness

15. Obesity causes cancer in women  “The conversion of androstenedione secreted by the adrenal gland into oestrone by aromatose in adipose tissue provides an important source of oestrogen for the postmenopausal woman”. This oestrogen is thought to play an important role in the development of endometrial and breast cancer. (Eddy 2005) • High carbohydrate consumption causes obesity  The body will choose to metabolise carbohydrates in preference to fats. However, instead of consuming more carbohydrates, remember that during carbohydrate feeding lipolysis is significantly reduced, therefore fat does not get broken down as needed. (Eddy 2005)

16. A Harvard Nurses study in 2000 found that a high intake of rapidly digested and absorbed carbohydrate increases the risk of coronary heart disease (CHD) and that the low fat, high carbohydrate diet may not be the best prevention of CHD and could be responsible for increasing the risk in individuals with insulin resistance and glucose intolerance. (Eddy 2005) Therefore low GI/GL foods are of value • There is an increasing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggesting that a diet that induces high blood glucose levels and an elevated insulin response may contribute to a metabolic environment that is conducive to tumour growth. (Eddy 2005)

17. Insulin stimulates pathways that increase levels of insulin-like growth factor, and both insulin and insulin-like growth factor promote mitosis and cell proliferation but inhibit apoptosis in normal and cancer cells of the colonic epithelium. (Eddy 2005) • What is actually is actually happening with our dietary habits in the 21st Century? (Eddy 2005) • Major movement towards “low fat”  however • Often high in carbs / sugar • Lacking in satiety • Larger portion required and craved • Increase in convenience foods • Usually both high carbohydrate and high fat • Highly processed foods increase the amount of trans fats consumed • Low in nutrients

19. IMPLICATIONS OF THESE FACTS FOR YOU IN CLINICAL PRACTICE ARE? • WHAT WILL YOU BE ADVISING YOUR CLIENTS? WHY?

20. More revision – what is white fat and brown fat and how do they differ? And how do we benefit from an understanding of how adipose tissue works when trying to explain the obesity epidemic? • There are two types of adipose tissue • White adipose tissue (unilocular) is coloured white or yellow and has relatively few nerves and blood vessels • Each fat cell contains a single large droplet of triglyceride that is coated with a protein called perilipin • White fat is used as a site for storing energy for physical activity • Leptin is generally produced in white fat

22. Brown adipose tissue (multilocular) contains more nerves and blood vessels • Each brown fat cell contains several small droplets of triglyceride, rather than one large one. • Brown fat is used for heat production • Levels decrease with age but is still detectable in the 6th decade

24. Excess adipose tissue, especially white fat, leads to reduced insulin sensitivity in metabolically responsive tissues, which is frequently associated with a set of cardiovascular risk factors, including hyperinsulinemia, hypertension, dyslipidemia and glucose intolerance.

25. Therefore, our aim would be to increase the levels of brown adipose tissue  ↑thermogenesis  ↑metabolic rate and energy consumption  the burning of white fat

26. Several molecules secreted by adipose tissue play a critical role in this process of increasing metabolic rate: • Adiponectin • Leptin • Resistin • Interleukin 6

27. HOW? • Adiponectin  • ↑insulin sensitivity • ↓ glucose • Stimulates lipid catabolism • Leptin  • ↓glucose, insulin and lipids • Stimulates lipid oxidation

28. LEPTIN • Refer to page 340 – 1 of McGuire and Beerman and come to an understanding of the role that the hormone Leptin plays in obesity. • Rats without functional leptin receptors and mice without functional leptin proteins (ob/ob) both exhibit characteristics of morbid obesity, insulin resistance, delayed or impaired pubertal development, and pituitaries with low numbers of somatotropes or gonadotropes. (Crane,C., Akhter,N., Johnson,B et al.2007, ‘Fasting and glucose effects on pituitary leptin expression. Is leptin a local signal for nutrient status?’Journal of Histochemistry Cytochemistry, vol.55, iss.10, pp.1059–1073) • Increased leptin in patients with lipodystrophy results in less caloric, shorter, more satiating meals and longer lived satiety. These data support the hypothesis that leptin plays an important, permissive role in human appetite regulation. (McDuffie,J., Riggs,P., Calis,K et al. 2004, ‘Effects of Exogenous Leptin on Satiety and Satiation in Patients with Lipodystrophy and Leptin Insufficiency’, Journal of Clinical Endocrinology and Metabolism, vol.89, iss.9, pp.4258–4263)

29. Leptin controls energy uptake and use by regulating various satiety factors in the hypothalamus, such as neuropeptide Y or glucagon-like peptide 1. Since leptin is synthesised in white adipocytes, fat mass functions as a central control sensor. (Biesalki & Grimm 2004 p.37) • When leptin is injected into leptin deficient animals, it results in decreased food intake and subsequent weight loss and the maintenance of weight loss. Obese humans do not have a deficiency of leptin, but surprisingly have higher levels of circulating leptin in the body. This would indicate that leptin deficiency is not a primary cause of obesity, but rather a decreased response to leptin.... In patients with morbid obesity, an increase in leptin production by the enlarged fat mass would be Futile. (Wilborn,C., Beckham,J., Campbell,B. Et al. 2005, ‘Obesity: Prevalence, Theories, Medical Consequences, Management, and Research Directions’ Journal of the International Society of Sports Nutrition, vol.2, iss.2, pp.4–31)

30. Page 346 - 7 of McGuire and Beerman discusses the role of leptin and insulin in the development of obesity. • After reading through this information and following the 2 pathways in figure 9.13 discuss ways you can use this knowledge with your obese / overweight clients. • Find a way of summarising this process in a way that your clients will understand.

31. Adiponectin • Adiponectin is an adipose cell messenger (adipocytokine) and is the link between obesity and insulin resistance. It is secreted by adipose tissue and circulated in the blood. • Adiponectin concentrations correlate strongly with the concentration of HDL cholesterol and LDL particle size. • As an insulin sensitizer, adiponectin is shown to enhance insulin sensitivity through increases in fatty acid oxidation and insulin-mediated glucose disposal as well as decreases in hepatic gluconeogenesis and glucose output.

32. It has also been shown that the role of adiponectin in positively influencing HDL and triglyceride levels is attributed to adiponectin-induced activation of the transcription factor peroxisome proliferator-activated receptor-alpha (PPAR-a) which lowers triglycerides and increases HDL by increasing the expression of genes involved in metabolism of lipids and apolipoproteins • Patel et al 2006; Fruchart et al 2001; Yamauchi et al 2003

33. Kadowaki

34. There is increasing evidence for a causal link between adiponectin and insulin sensitivity that is medicated via receptors that promote glucose uptake and metabolism in the liver. (Singhal et al 2005)

35. Adiponectin levels are, on the average, considerably higher in women than men and women and men have a marked difference in body fat distribution. • Because adiponectin is secreted by adipocytes and is closely related to glucose metabolism and given the sex differences in these risk factors, its effect on CHD differs between men and women. (Lawlor et al 2005) • in skeletal muscle adiponectin has been shown to ↓ tissue triglyceride content by ↑ utilisation of fatty acids as a fuel source

36. Cnop 2003

37. Cnop 2003

38. THEREFORE - ADIPONECTIN: ↓Hepatic glucose output ↑Fatty acid oxidation in muscle and liver With an overall ↓ in triglycerides

39. AND Adiponectin: Reduces central fat accumulation AND Low adiponectin levels may induce alterations in the insulin response

40. What is PPAR-а and ỵ • Peroxisome proliferator-activated receptor (PPAR) [pronounced p-par] are nuclear hormone receptors that, when activated, exert different functions and plays a key role in the regulation of genes involved in carbohydrate, lipid and lipoprotein metabolism • There are 3 PPAR subtypes • Gamma (y) • Alpha (a) • Delta (δ) Grundy

41. PPAR-y is highly expressed in adipocytes where it mediates cell differentiation and promotes lipid storage • Activation of PPAR-y results in improved insulin sensitisation and enhanced glucose disposal in adipose tissue and skeletal muscle Grundy

42. PPAR-y agonists acts by improving lipid and insulin function by sequestering lipid within the triglyceride droplet in adipose tissue • It is believed that this will protect skeletal muscle, liver and beta cells (from the pancreas) from excess lipid supply • PPAR-y agonists act by • Decreasing Free Fatty Acids (FFA’s) in the blood • Increasing insulin stimulated lipid storage

43. PPAR-a is activated by polyunsaturated fatty acids and is implicated in • the regulation of lipid metabolism • lipoprotein synthesis and metabolism • an inflammatory response in liver and other tissues • Activation of PPAR-a results in • decreased plasma levels of triglycerides • increased plasma HDL cholesterol levels • May stimulate reverse cholesterol transport

44. http://www.lejacq.com/Symposia_Info/UMH_NY-0306/Giles.ppt#23

45. HOW? • 4-wk supplementation of conjugated linoleic acid (CLA) showed a significant reduction of serum leptin concentration (42%) ..... As well there was a 5.2% decrease in body weight..... CLA enhanced activity in brown adipose tissue ..... (Rahman,S. Et al. 2001, ‘Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and β-oxidation of fatty acid in OLETF rats’, Nutrition, vol.17, iss.5, pp.385 - 390) • Dietary Conjugated Linoleic Acid supplementation has resulted in a dramatic decrease in body fat mass in mice..... decreased the blood glucose and insulin levels, and improved insulin resistance..... reduced weight gain and perigenital fat pad weight..... Can reduce leptin levels. (Zhou,XR., Sun,CH, et al 2008, ‘Dietary conjugated linoleic acid increases PPARy gene expression in adipose tissue of obese rat, and improves insulin resistance’, Growth Hormone & IGF Research)

46. Refer back to earlier revision and to page 326 McGuire and Beerman to discuss how best to ↑thermogenesis • In this study it was found that irregular meal frequency led to a lower postprandial energy expenditure compared with the regular meal frequency, while the mean energy intake was not significantly different between the two. The reduced TEF (thermal effect of food) with the irregular meal frequency may lead to weight gain in the long term. (Farshchi,HR., Taylor,MA., Macdonald,IA. 2004, ‘Decreased thermic effect of food after an irregular compared with a regular meal pattern in healthy lean women’, International Journal of Obesity and Related Metabolic Disorders, vol.28, iss.5, pp.653-60)

47. In this study, it was found that regular eating was associated with lower Energy Intake, greater postprandial thermogenesis, and lower fasting total and LDL cholesterol. Fasting glucose and insulin values were not affected by meal pattern, but peak insulin concentrations and area under the curve of insulin responses to the test meal were lower after the regular than after the irregular meal pattern. It was therefore concluded that regular eating has beneficial effects on fasting lipid and postprandial insulin profiles and thermogenesis. (Farshchi,HR., Taylor,MA., Macdonald,IA. 2005, ‘Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women’, American Journal of Clinical Nutrition vol.81, iss.1, pp.16-24)

48. Green tea has been shown to increase Resting Energy Expenditure by 372kJ/day, or about one-fourth of moderate exercise..... There is evidence that green tea polyphenols depress leptin levels ..... the consumption of green tea extract elevates both the metabolic rate and the rate of fat oxidation ..... In conclusion, green tea capsules in a dosage of 100mg/day EGCG can increase energy expenditure and fat oxidation in obese subjects in 12weeks period. (Auvichayapat,P., Propochanung,M et al 2008, ‘Effectiveness of green tea on weight reduction in obese Thais: A randomised, controlled trial’, Physiology & Behaviour, vol.93, iss.3, pp.486-491)

49. Carbohydrates inhibit leptin  The postprandial leptin response is lower after a carbohydrate meal in obese women than in lean controls, suggesting an impairment of postprandial leptin regulation in obese women. (Eddy 2005) • Triglycerides cause leptin resistance  Triglycerides are an important cause of leptin resistance as mediated by impaired transport across the BBB and suggest that triglyceride-mediated leptin resistance may have evolved as an anti-anorectic mechanism during starvation. Decreasing triglycerides may potentiate the anorectic effect of leptin transport across the BBB. (Eddy 2005) • Insulin reduces leptin  overweight and obese PCOS subjects appear to produce insufficient leptin for a given fat mass and this was found to be relative to the degree of hyperinsulinaemia, potentially because of the leptin reducing effects of adipocyte insulin resistance. (Eddy 2005)

50. Other nutritional considerations that must be considered when dealing with obesity are: • Alpha-lipoic acid  • up regulates ppar to grab fatty acids and take them out of the bloodstream • Regenerates nutrients and reduces oxidative stress • The type of fat, rather than the amount of fat, in the diet may be more important in terms of determining health outcomes. Many studies have shown that the long chain n-3 polyunsaturated fatty acid found in oily fish and fish oil possess cardioprotective effects and α-lipoic acid possesses antioxidant property with improving insulin sensitivity. (Wu,CJ & Yu,ZR. 2004, ‘Effects on blood glucose, insulin, lipid and proatherosclerotic parameters in stable type 2 diabetic subjects during an oral fat challenge’, Lipids in Health and Disease, vol.3, iss.17)