PUSAT LAPAR & KENYANGPENGATURAN PEMASUKAN MAKANAN

PEMASUKAN MAKANAN?Berapa kali sehari kita makan?Apa yang mendorong kita makan?Apa saja yang kita makan?Tujuan apa yang dicapai dengan pemasukan makanan?Adakah bahaya makanan bagi tubuh?

BERAPA KALI SEHARI KITA MAKAN?Pengaruh selera?Pengaruh keuangan?Pengaruh aktivitas?Pengaruh emosi?

APA YANG MENDORONG KITA MAKAN?Rasa lapar/kenyang?Di mana pusatnya?Apa yang merangsang?Bagaimana prosesnya?Apa efektornya?Bagaimana relasinya dng sistem di tubuh?

Adapted from R. Unger2.5 milion of years50 yearsThe progression of mankind development

Historical view of the regulation of food intakeLipostatic hypothesis (Kennedy 1953) adipose tissue produces specific lipostatic factor

Glucostatic hypothesis (Mayer and Thomas 1967) fluctuations in glycaemia lead to stimulation/inhibition of food intake (regulating organs brain and the liver)

Combination of above mentioned

The physiological regulation of food intake is a complex homeostatic process that is regulated by many endocrine and metabolic factors in a combination with visual, olfactory, taste sensation, emotions, memory and the life conditions

The balance between energy intake and expenditure is tightly regulated and body weight is stable despite day-to-day food intake fluctuations......

..but when the border is overestimated the balance is broken.

Interactions between emotions and metabolic/endocrine regulationsBerthoud et al. 2006

Genetic backgroundFood intakeEnergyexpenditureLife stylHypotalamic satiety centre(neuropeptides, leptin, insulin)Sympathetic nervous system- Energy expenditure, lipolysisGastrointestinal tractghrelin, peptide YYAdipose tissueleptin, adiponectin, resistin, TNF-a

Hypothalamus and brain stem are crucial in central regulation of feedingIntegration of brain neurotransmiters, peripheral neurohumoral afferents, adipocyte-derived signals, GIT peptides

N. arcuatus (ARC) receptors for hormones and neuropetides that regulate feeding

N. paraventricularis (PVN) integration of signals from ARC with thyroid and HPA axes

N. vagus satiety signals to the brain stem after ingestion of a meal

N. tractus solitarius + PVN connection of brainstem with hypothalamus (serotoninergic neurons)Modulated by neocortexSource: Morton et al. 2005

HypothalamusVentromedial nuclei satiety centre (lesion leads to hyperfagia)

Lateral nuclei hunger centre (lesion leads to anorexia)

N.arcuatus pivotal role in the integration of signals regulating appetite

N. suprachiasmaticus timing (lesions in humans lead to night hyperfagia and obesity

Energy homeostasis is controlled by peripheral signals from adipose tissue, pancreas, and the GIT. Gut-derived peptides and adiposity signals influence central circuits in the hypothalamus and brain stem to produce a negative () or positive (+) effect on energy balance. Thus the drive to eat and energy expenditure are adjusted so that over time, body weight remains stable.

Adipose tissue plays an important role in the regulation of energy homeostasis

Factors regulating food intake

SATIETY FACTORSHUNGER FACTORSStomach and duodenum distension (n.vagus)Hungry contractionsheatcold glucose, amino acids, lipids in blood glucose, amino acids, lipids in bloodcatecholaminesorexinsserotoninendorphinsACTHGalaninInsulin (food in stomach)Glutamic acidLeptincortisolCCK (lipids in duodenum)Neuropeptide YMSHGABAglucagonghrelinPeptide YYAMPK

APA SAJA YANG KITA MAKAN?Macam makanan?Sumber tenaga?Sumber bahan bangunan?Sumber bahan pengatur?Sumber bahan pelarut/media reaksi kimia?

TUJUAN APA YANG DICAPAI DENGAN PEMASUKAN MAKANAN?Kenyang?Puas?Pemenuhan kebutuhan tubuh?

ADAKAH BAHAYA MAKANAN BAGI TUBUH?Tidak ada bahayanya?Ada bahayanya?Apa saja bahayanya?Bagaimana mencegah/menanggulangi bahaya makanan?

OBESITY

Obesity is classified by Body Mass Index (BMI)BMI =

Waist circumference is a helping indicator of visceral fat this fat is the most metabolically active and thus the most harmful

Complications of obesityMechanical joint illness, dyspnoe, sleeping apnoe, heart hypetrophy,..

Metabolic - diabetes, hypertension, hyperlipoproteinemia, ischemic heart disease, ictus, tumours, sterility, depression,.. = Reaven metabolic syndrome

More slim and more fit means more success and beauty.. .. but sometimes this motto of modern societies leads to death

Anorexia Nervosa (AN)Severe psychiatric disorder of unclear etiology associated with significant morbidity and mortality (Hsu 1996)

Prevalence 0.3% of young girls, mortalty of 6%/decade (Dardeness 2007)

Irrational fear of becoming fat even if patient is of normal or usually underweight

Phobic response to food, abnormal eating behavior, hyperactivity, weakness, muscle aches, sleep disturbances, GIT complications, mood disturances, alterations of wide variety of hormonal and metabolic systems

Combination of cultural-social, psychological, biological factors

Complications of ANHematological and electrolyte: leukopenia with leukocytosis, alkalosis, hypokalemia, hypochloremia, elevated serum bicarbonate (vomiting), acidosis (laxatives), dehydration, lethargy, weakness

Chemistry: elevated liver enzymes, elevated serum cholesterol, carotinemia, elevation of amylase (vomiting)

GI: delay in gastric emptying sense (pp discomfort-early satiety-restricting behavior cycle), gastritis, esophageal erosions (vomiting) or rupture (binge eating)

Long-term complications: OsteoporosisAmenorrhea - persisting after weight recovery in 50% of AN (warren and Vande Wielle 1973)Skeletal-muscular injuries (sprains, fractures)

Cancer anorexiaCancer anorexia-cachexia syndrome (Tisdale 1997)Observed in 80% of advaced-stage cancerOne of the most frequent causes of death (Mantovani 2001)The role of proinflammatory cytokines (serotonin) released by cancer cells or immune systm in inducing satiety and anorexia, activation of anorexigenic pathway

Regulation of the feeding in cancer patientsAnorexia satietyinhibition

*But these genes outlasted in our genetical information to date, although in modern societies these genes are rather harmful than useful and may contribute to the development of obesity.

*Now we are back in the present and we are asking how we can define the physiological regulation of food intake?...definition.....we will not talk about the outer influences, feelings, but we have to bear in mind that these factors are really important in a modulating of a final feeling of hunger and satiety. Physiologically, the regulation of food intake lies in the interplay of short-term satiety signals evoked by the presence of nutrients in the GIT with long-term signals that reflect fat depots in organism. *It means that in spite of day-to-day fluctuations in food intake the body weight remains stable. However, when the border is overestimated, body starts to gain or loss the weight. In other words when the energy expenditure is highly inequal to energy intake, the body is not able to compensate too high deviations.*It is not only the balance between food intake and energy expenditure what contributes to energy homeostasis, but the energy homeostasis centrally integrated mainly in hypothalamus and brain stem is especially in humans influenced in a higher level by emotions and stress situations and by learned feelings (you are not able to eat a milk soup that you vomited before 20 years in the school). However, why some people under stress eat a lot to feel better and some can not eat anythink??? The explanation lies in the different relative and absolute levels of hormones and different sensitivity to their actions together with genetical background.*Especially in humans all regulations are under tight control of higher centres (neocortex) and so called will can dramatically influence mood and feelings associated with eating. The classical example are patients with AN, who usually are hungry but they dont eat because they dont want to. However, what is the will not to eat? It lies in the disrupted balance of levels of hormones and neurotransmitters acting in brain as we will be talking about later.*Lets go back to some classical theory. We know that the central part of the food intake regulation is situated mainly to hypothalamus and brain stem. These are the places where short-term signals from GIT and long-term signals from adipose tissue are integrated and the final response is produced.The majority of peripheral hormones acting in energy homeostasis regulation acts in ncl. Arcuatus. From arcuatus the signal is transported to n. PVN and integrated with thyroid (metabolism) and adrenal axes (stress). N. vagus is on the other side the main way of how hormones from GIT mediate their acute signals of satiety to the brain. Finally, n.tractus solitarius represent the connection of brainstem (short-term signals) with signals from hypothalamus (long-term signals).*I only want to mention that originally, hypothalamic nuclei had been divided in two groups: satiety centre and hunger centre. However, under the actual knowledge this is not the precise description. I would prefer that both anorexigenic and orexigenic signals are integrated in hypothalamus and the final response is directly proportional to the relative distribution, activity and receptors for signals of satiety and hunger. What is undouptebly true is the fact that n.arcuatus plays a pivotal role in the integrations of signals regulating appetite. Almost all hormones that we will be talking about act at least partly in the ARC where the receptors for them are situated.*To time, our talk was focused predominantly on the central part of food intake regulation, although as you saw the human body functions as a unit and it is difficult and probably not very good to talk about the parts of it without seing the relationships. Now we have to say again that E homeostasis is controlled by peripheral signals from.......*Adipose tissue has been considered as a passive storage of triglycerides for a long time. However, this tissue is very important for energy homeostasis and both the excess and deficiency of it have dramatic metabolis consequences.

*Here is a overview of components of food intake regulation. You probably know the classical glucostatic or lipostatic theory. It is not surprising that when it is cold you eat more, macronutrients are stimulus for secretion of GIT and pancreatic hormones. About the hormonal regulations we will be talking later. Catecholamines as markers of the activity of autonomic nervous system are well known. Cortisol as a part of stress HPA axis is known. What is however interesting is the AMPK.*All I said to time was true for physiological regulations. Now we start to talk about the main pathophysiological points of neurohormonal regulation of food intake in obese subjects.*3

Xenical Slide Kit August 1998 Section 13How we can classify that somebody is obese?The most simple is to get its weight and height and calculate so called body mass index. Its value more than 30 means obesity and less than 18 is one of the diagnostic criterium for anorexia nervosa. Of course the other classification is to measure percent body fat by anthropometry, bioimpedancy etc., but it is more complicated.*5

Xenical Slide Kit August 1998 Section 15Waist circumference is a very useful indicator of visceral fat amount, this type of fat triggers the obesity-associated complications such as insulin resistance. We will be talking about this in detail in the next lecture*15

Xenical Slide Kit August 1998 Section 115The complications of obesity are as follows:*Paradoxical increase of the prevalence of anorexia nervosa in last decades is highly alarming*AN is a severe psychiatric disorder leading to life-threatening weight and fat loss. This illness could be characterized by irrational fear of becoming fat, abnormal eating behavior, hyperactivity, GIT complications and wide variety alterations of hormonal and metabolic systems, the exct etiopathogenesis is unknown and the way of treatment remain limited*As expected AN is associated with many acute and chronic complications. Acute complications include hematological, biochemical and electrolyte abnormalities and Gi complications. The most harmful chronic comlications of AN are osteoporosis, amenorrhea and inability to become pregnant and skelatal-muscle injuries.*And shortly before we will finish I would like to very briefly mention one specific type of anorexia in cancer anorexia-cachexia syndrome. *In this process there is an important role of proinflammatory cytokines released by cancer and immune cells in inducing satiety and anorexia in cancer patients.High levels of cytokines in association with high serotonin act in hypothalamus to decrease NPY release and increase POMC release leading to inhibition of hunger