Body nutrient status –Informing the brain about body energy stores Flashcards

(48 cards)

1
Q

Neuronal Networks in Obesity
what do organised neuronal networks in obesity encode signals about

A

organised neuronal networks on obesity encode signals about energy stores, food intake (amount and type) and immune satus (microbiome)

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2
Q

Integrated Outputs in Obesity
How do various networks in obesity independently modulate ANS output to peripheral organs

A

various networks in obesity independently modulate autonomic nervous system (ANS) output to peripheral organs, including fat, liver, pancreas, spleen etc.

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3
Q

Defective Nutrient Partitioning
what is proposed as a mechanism driving obesity-related morbidities beyond food intake?

A

defective nutrient partitioning, independent of food intake, is suggested as a mechanism driving obesity-related morbidities

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4
Q

Bi-directional flow of Information in CNS
Is the flow of information between CNS centers and peripheral organs unidirectional or bidirectional

A

The flow of information between CNS centers and peripheral organs is bidirectional

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5
Q

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

A

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

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6
Q

Humerol Signals from Peripheral Organs
What do humoral signals generated by peripheral organs convey, and which orans contribute to long-term memory balance?

A

Humoral signals convey information about body energy stores for long-term energy balance. These signals mainly derive from the pancreas and adipose tissue

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7
Q

Factors in Regulation of Food Intake
What are three factors that underlie regulation of food intake?

A

The three factors undelying the regulation of food intake are satiety signaling, adiposity negative feedback signaling and food reward

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8
Q

Short Term Processes in Food Intake
what do short term processes regulate in terms of food intake

A

short term processes regulate meal initiation, termination, and inter-meal frequency

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9
Q

Satiation and Satiety Signals
What are some satiation and satiety signals in the CNS

A

Satitaion signals increase during a meal to limit meal size. Eamples include CCK, PYY3-36, GLP-1, oxyntomodulin (OXM) and Obestatin

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10
Q

Monogenic Obesity Impact
WHat transformation did the cloning of genic loci associtaed with monogenic obesity syndromes bring to the field of energy regulation

A

the cloning of the loci has significantly transofrmed our understanding of energy regulation

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11
Q

ob/ob mouse traits
describe the traits of the ob/ob mouse traits

A

ob/ob mice are obese, hyperphagic, hyperinsulinaemic, hyperglycaemic, and insulin resistant due to the lack of circulating leptin

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12
Q

db/db mouse traits
what traits characterise db/db mice, and what is the genetic basis of their obesity

A

db/db mice are profoundly obese, hyperphagic and overtly diabetic, they lack functional leptin receptors due to a genetic mutation

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13
Q

biological roles of leptin
what happens in mice lacking leptin or its receptor

A

mice lacking leptin or its receptor exhibit morbid obesity, hyperphagia, decreased energy expenditure, insulin resistance, hyperglycaemia, and metabolic dysfunction

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14
Q

CNS Actions of Leptin
How does leptin act in the central nervous system (CNS)

A

In the CNS, leptin reduced gluconeogenesis, glycogenolysis, and suppresses lipogenesis in white adipose tissue, contributing to metabolic regulation

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14
Q

Plietropic actions of leptin
what are some non-metabolic roles of leptin in mice

A

leptin is involved in regulating puberty onset, enhancing angiogenesis, influencing other hormone actions, contributing to immune responses and potentially impacting tumorigenesis

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15
Q

Importance of Leptin
How important is leptin in physiological processes

A

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

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16
Q

Leptin Receptor Variants
what are charcteristics of the leptin receptor gene

A

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

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17
Q

Circulating Leptin Levels
How do circulating leptin levels correlate with adipose tissue mass

A

circulating leptin levels are highly correlated with adipose tissue mass, fluctuiating with nutritional states such as decreased levels during fasting

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18
Q

Leptin Resistance
In cases of chronic high-fat-diet induced obesity what is often associated with high levels of circulating leptin

A

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

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19
Q

Leptin and glucose homeostasis
Does leptin have metabolic effects independently of body weight reduction

A

Yes, leptin has metabolic effects independently of body weight reduction

20
Q

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

A

Hyperinsulinaemia precedes obesity in ob/ob and db/db mice and it precedes the action of leptin

21
Q

Low Leptin Dose Effects
what effects does a low dose (1mg/kg/day) have in ob/ob mice?

A

A low leptin dose does not lower body weight but reduces blood glucose and insulin levels in ob/ob mice

22
Q

Leptin Antagonist Effects
WHat happens when a leptin antagonist is given, and what does it affect first?

A

A leptin antagonist raises blood glucose and insulin levels before a change in body weight

23
Q

Leptin Therapy in INsulin Deficient Rodents
How does leptin therapy affect insulin-deficient rodents with depleted WAT

A

Leptin therapy reverses hyperglycaemia, hyperphagia, and insulin resistance in insulin deficient rodents with depleted white adipose tissue

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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
25
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
26
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
27
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
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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
29
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
30
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
31
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
32
Leptin and Angiogenesis How is leptin involved in ANgiogenesis
Leptin has been reported to enhance Angiogenesis, contributing to the formation of new blood vessels
33
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
34
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
35
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
36
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
37
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
38
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
39
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
40
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
41
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
42
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
43
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
44
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
45
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
46
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
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