Body nutrient status –Informing the brain about body energy stores Flashcards
Neuronal Networks in Obesity
what do organised neuronal networks in obesity encode signals about
organised neuronal networks on obesity encode signals about energy stores, food intake (amount and type) and immune satus (microbiome)
Integrated Outputs in Obesity
How do various networks in obesity independently modulate ANS output to peripheral organs
various networks in obesity independently modulate autonomic nervous system (ANS) output to peripheral organs, including fat, liver, pancreas, spleen etc.
Defective Nutrient Partitioning
what is proposed as a mechanism driving obesity-related morbidities beyond food intake?
defective nutrient partitioning, independent of food intake, is suggested as a mechanism driving obesity-related morbidities
Bi-directional flow of Information in CNS
Is the flow of information between CNS centers and peripheral organs unidirectional or bidirectional
The flow of information between CNS centers and peripheral organs is bidirectional
Satiety Signals in CNA
What controls meal size in the CNS, and what are the signals from upper GI tract via vagus and sympathetic afferents
Satiety signals control meal size, and information from the upper GI tract tract via vagus and sympathetic afferents converges on the nucleus of the solitary tract (NTS) and hypothalamus
Humerol Signals from Peripheral Organs
What do humoral signals generated by peripheral organs convey, and which orans contribute to long-term memory balance?
Humoral signals convey information about body energy stores for long-term energy balance. These signals mainly derive from the pancreas and adipose tissue
Factors in Regulation of Food Intake
What are three factors that underlie regulation of food intake?
The three factors undelying the regulation of food intake are satiety signaling, adiposity negative feedback signaling and food reward
Short Term Processes in Food Intake
what do short term processes regulate in terms of food intake
short term processes regulate meal initiation, termination, and inter-meal frequency
Satiation and Satiety Signals
What are some satiation and satiety signals in the CNS
Satitaion signals increase during a meal to limit meal size. Eamples include CCK, PYY3-36, GLP-1, oxyntomodulin (OXM) and Obestatin
Monogenic Obesity Impact
WHat transformation did the cloning of genic loci associtaed with monogenic obesity syndromes bring to the field of energy regulation
the cloning of the loci has significantly transofrmed our understanding of energy regulation
ob/ob mouse traits
describe the traits of the ob/ob mouse traits
ob/ob mice are obese, hyperphagic, hyperinsulinaemic, hyperglycaemic, and insulin resistant due to the lack of circulating leptin
db/db mouse traits
what traits characterise db/db mice, and what is the genetic basis of their obesity
db/db mice are profoundly obese, hyperphagic and overtly diabetic, they lack functional leptin receptors due to a genetic mutation
biological roles of leptin
what happens in mice lacking leptin or its receptor
mice lacking leptin or its receptor exhibit morbid obesity, hyperphagia, decreased energy expenditure, insulin resistance, hyperglycaemia, and metabolic dysfunction
CNS Actions of Leptin
How does leptin act in the central nervous system (CNS)
In the CNS, leptin reduced gluconeogenesis, glycogenolysis, and suppresses lipogenesis in white adipose tissue, contributing to metabolic regulation
Plietropic actions of leptin
what are some non-metabolic roles of leptin in mice
leptin is involved in regulating puberty onset, enhancing angiogenesis, influencing other hormone actions, contributing to immune responses and potentially impacting tumorigenesis
Importance of Leptin
How important is leptin in physiological processes
Leptin is crucial, as seen in ob/ob mice where it rapidly restores glycaemic control independently of food intake. It plays a key role in various physiological functions
Leptin Receptor Variants
what are charcteristics of the leptin receptor gene
The leptin receptor gene has multiple splice variants (LEP-Ra to LEF-Rf). LEP-Rb is the longest variant and is abundant in the hypothalamus
Circulating Leptin Levels
How do circulating leptin levels correlate with adipose tissue mass
circulating leptin levels are highly correlated with adipose tissue mass, fluctuiating with nutritional states such as decreased levels during fasting
Leptin Resistance
In cases of chronic high-fat-diet induced obesity what is often associated with high levels of circulating leptin
leptin resistance, often associated with high levels of circulating insulin and peripheral insulin resistance, is observed in cases of chronic high fat diet induced obesity
Leptin and glucose homeostasis
Does leptin have metabolic effects independently of body weight reduction
Yes, leptin has metabolic effects independently of body weight reduction
Hyperinsulinaemia in ob/ob and db/db mice
What precedes obesity in ob/ob and db/db mice, and how dies it relate to leptin
Hyperinsulinaemia precedes obesity in ob/ob and db/db mice and it precedes the action of leptin
Low Leptin Dose Effects
what effects does a low dose (1mg/kg/day) have in ob/ob mice?
A low leptin dose does not lower body weight but reduces blood glucose and insulin levels in ob/ob mice
Leptin Antagonist Effects
WHat happens when a leptin antagonist is given, and what does it affect first?
A leptin antagonist raises blood glucose and insulin levels before a change in body weight
Leptin Therapy in INsulin Deficient Rodents
How does leptin therapy affect insulin-deficient rodents with depleted WAT
Leptin therapy reverses hyperglycaemia, hyperphagia, and insulin resistance in insulin deficient rodents with depleted white adipose tissue
Lipodystrophy and Leptin Therapy
What is lipodystrophy and Leptin Therapy
What is lipodystrophy and how does leptin impact patients with this condition
Lipodystrophy is a condition where individuals lack fat cells. Leptin therapy in severe lipodystrophy improves insulin sensitivity, reduces fat in the liver and muscle, and decreases circulating fat levels
CNS targets of Leptin
What happens when the ARC (arcuate Nucelus) is destroyed, and how is LEP-Rb localised in the CNS
Destruction of the ARC eleminates the satiety response to Leptin. LEP-Rb is strongly localised to ARC neurons, inclduong NPY/AgRP and POMC/CART neuro ns
Leptins affect on Neuropeptide mRNA levels
How does elptin impact neuropeptide mRNA levels in fasting or leptin-resistant mice?
Leptin administartion directly reverses changes in neuropeptide mRNA levels induced by fasting or leptin resistance
Leptin’s impact on synaptic Plasticity
How does leptin deficiency affect brain size and synaptic connections in ob/ob mice
Leptin deficiency reduce brain size and alters synaptic connections in ob/ob mice
Diet and Hormones altering ARC neuron SYnaptic PLasticity
How does diet and hormones alter synaptic plasticity in ARC neurons
Diet and hormones influence synaptic plasticity in ARC neurons, affecting growth of neurites and synaptic connections
Leptin and Diabetes in ob/ob mice
What does leptin therapy achieve in ob/ob mice rearding diabetes
leptin therapy in ob/ob mice rapidly restores glycaemic control, independent of food intake
CNS leptin and Metabolic Functions
what are the metabolic functions of CNS leptin
CNS leptin reduces gluconeogenesis, glycogenolysis, and suppresses lipogenesis in white adipose tissue
Leptin’s role in Puberty Onset
WHat role does leptin play in regulating the onset of puberty
Leptin is essential in regulating the onset of puberty, and its deficiency delayes puberty
Leptin and Angiogenesis
How is leptin involved in ANgiogenesis
Leptin has been reported to enhance Angiogenesis, contributing to the formation of new blood vessels
Leptin’s impact on Bone Growth
How does leptin influence bone growth in ob/ob mice
Ob/Ob mice lacking leptin ecperience reduced bone growth, and leptin administartion corrects its defieciency
Importance of Leptin in Reproductive System
Why is leptin important for reproductive systems
leptin is required for normal function in immune and reproductive systems and it plays a role in enhancing angiogenesis
Leptin Receptor (LEP-R) VAriants
What are the variants of the leptin receptor (LEP-R)
LEP-R mRNA has multiple splice variants with LEP-Rb being the lomgest and having intracellular otifs required for signaling
CNS targets of Leptin and Food Intake
What happens to food intake when the ARC is destroyed, and how does LEP-Rb impact obesity
Destruction of the ARC eliminates the satiety response, and restoration of LEP-Rb to the C NS reduces obesity, hyperphagia, and hyperglycaemia
Leptins imapct on Brain size
How does leptin deficiency affect brain size in miceLepti
Leptin deficiency reduces brain sixe and disrupts projection pathways between ARC and PVN
Leptin Therapy in Lipodystrophy
What are the outcomes of leptin therapy in Lipodystrophy patients
Leptin therapy in severe lipodystrophy improves insulin sensitivity, reduces fat in the liver and muscle, and decreases circulating fat levels
Hypothalamus and Insulin Delivery
How is insulin delivered to the hypothalamus, and what effects does it have
Insulin delivery to the hypothalamus, direct in rodents and intranasal in humans, modulates neuronal activity, improves whole-body insulin sensitivity, promotes lipogenesis, peripheral fat accumulation, and increases adaptive thermogenesis
Brain INsulin Resistance
What is associated with brain insulin resistance in obesity and diabetes
reduced levels in DIO dogs and genetically obese rats. Lower CSF/plasma insulin ration in insulin resistant humans, and impairment in proximal insulin signaling components in the hypothalamus of DOI and genetically obese rodents
Insulin’s role in ARC for HGP inhibition
how does insulin act in the ARC to reduce HGP production
Insulin acts in the ARC to inhibit gluconeogenesis, and reduced brain insulin signaling diminishes the ability of peripheral insulin to suppress HGP
Central Insulin and HGP
WHat is the contribution of central insulin to HGP
Central Insulin contributes to HGP, involving ARC, AgRP enurons, vagal efferents to the liver, and transduction via alpha7 nicotinic receptors and IL-6
Insulin and Leptin Regulation of ARC neurons
How do leptin and insulin regulate ARC neurons
Leptin and Insulin, expressed on ARC neurons, increase POMC mRNA and decrease NPY/AgRP mRNA. They reduce NPY release, increase alphaMSH release, and their effects on ARC neuron electrical properties are similar
Leptin and Glucose Homeostasis
what are the metabolic effects of leptin independent of body weight reduction
leptin in ob/ob and db/db mice precedes, and low leptin dose reduces blood glucose and insulin levels without affecting body weight
Therapeutic Example of Leptin
Provide a therapeutic example of leptin’s effects in humans woth lipodystrophy
Leptin therapy in lipodystrophy improves insulin sensitivity, reduces fat in the liver and muscle, decreases circulating fat levels, lowers fasting blood glucose and restores ovulation in some women
CNS targets of Leptin
what happens if the ARC is destroyed, and how is LEP-Rb distributed in the hypothalamus
Destruction of ARC abolishes leptin’s reduction of food intake and LEP-Rb is strongly localised to ARN neurons, especiallyNPY/AgRP and POMC/CART
