Question 1

You are studying the responses of fat cells in culture to the addition of various pharmacologic compounds. You find that addition of a β-adrenergic agonist does not result in the expected change in mitochondrial proton gradients. This would indicate that there was most likely a defect in the function of which of the following?

A) adiponectin
B) adipose triglyceride lipase
C) fatty acid synthase
D) leptin
E) UCP1

UCP1

Accepted Answer

UCP1 (uncoupling protein 1) is involved in the regulation of mitochondrial proton gradients. A defect in UCP1 function would prevent the expected changes in mitochondrial proton gradients in response to β-adrenergic agonists.  Norepinephrine binding to brown adipocytes triggers the activation of adenylate cyclase and the production of cAMP that in turn activates PKA. PKA phosphorylates and activates hormone-sensitive lipase, HSL. Activation of HSL leads to release of free fatty acids which are taken up by the mitochondria, similarly as they would be for purposes of oxidation; however, in BAT they interact with and activate the proton gradient uncoupling activity of uncoupling protein 1 (UCP1). Uncoupling the proton gradient releases the energy of that gradient as heat.

Question 2

Experiments have been designed to assess the effects of a novel drug on the inflammatory responses of adipose tissue in laboratory mice. Addition of the drug to the diet of the mice demonstrates a clear reduction in the production and release of pro-inflammatory cytokines from adipose tissue. This experimental drug is most likely inhibiting the action of which of the following leading to the observed results?

A) adiponectin
B) leptin
C) monocyte chemotactic protein-1, MCP-1
D) vascular cell adhesion molecule-1, VCAM-1
E) vascular endothelial cell growth factor, VEGF

monocyte chemotactic protein-1, MCP-1

Accepted Answer

The reduction in pro-inflammatory cytokines suggests that the drug is likely inhibiting MCP-1, which is involved in recruiting monocytes to sites of inflammation, thereby reducing inflammation in adipose tissue.  The significance of inflammatory responses elicited via secretion of adipose tissue- derived (WAT) cytokines relates to the fact that their production and secretion is increased in obese individuals. One key change in adipose tissue that results in increased synthesis and release of pro-inflammatory adipokines is an increase in the percentage of macrophages resident within the tissue. Macrophages are a primary source of pro-inflammatory cytokines secreted by adipose tissue. The primary adipokine responsible for this infiltration is monocyte chemotactic protein-1 (MCP-1). Thus, inhibition of MCP-1 releases or function would limit increased monocyte infiltration and reduce the pro-inflammatory actions of adipose tissue.

Question 3

The inflammatory activity of adipose tissue, particularly visceral fat, is enhanced in obese individuals. This effect of obesity is, in part, due to adipose tissue resistance to the actions of insulin. Insulin resistance in adipose tissue is reflected by a reduction in production of which of the following adipokines?

A) adiponectin
B) C-reactive protein, CRP
C) monocyte chemotactic protein-1, MCP-1
D) vascular cell adhesion molecule-1, VCAM-1
E) vascular endothelial cell growth factor, VEGF

adiponectin

Accepted Answer

Adiponectin is an adipokine whose production is reduced in the context of obesity and insulin resistance. It has anti-inflammatory and insulin-sensitizing properties, and lower levels are associated with increased inflammatory activity in adipose tissue.  Expression and release of adiponectin is stimulated by insulin; therefore, adiponectin levels are reduced in obese individuals primarily due to the loss of insulin-mediated stimulation. In patients with Type 2 diabetes, levels of adiponectin are also significantly reduced.

Question 4

You are studying the functions associated with adiponectin by utilizing site-directed mutagenesis of an adiponectin cDNA followed by expression of the cDNA in transgenic mice. One particular mutation abolishes nearly 100% of the activity of the protein but does not affect the level of protein found in the circulation of the test mice. This mutation most likely blocks which of the following modifications that is required for adiponectin function?

A) acetylation
B) glycosylation
C) phosphorylation
D) prenylation
E) ubiquitination

Accepted Answer

Glycosylation is a post-translational modification important for the proper folding, stability, and function of many proteins, including adiponectin. The mutation likely disrupts glycosylation, affecting the protein's activity without altering its circulating levels.  Adiponectin contains a C-terminal globular domain that allows for a homotrimeric association of the protein forming the functional structure of the protein. The hormone forms complex structures such that it can be found as a trimer, hexamer, and as the high-molecular-weight oligomer. In addition to the complex structure, adiponectin is glycosylated, a modification that is essential to its activity.

Question 5

The level of leptin that is secreted from adipose tissue increases with increasing fat deposits. Which of the following represents the major effect of leptin within the brain that is involved in overall lipid homeostasis on adipose tissue?

A) it activates AgRP neurons in the hypothalamus
B) it activates melanocortin neurons in the hypothalamus
C) it activates NPY neurons in the hypothalamus
D) it inhibits CART neurons in the brain stem
E) it inhibits insulin-responsive neurons in the brain stem

Accepted Answer

Leptin activates the anorexigenic axis (appetite suppression) in the arcuate nucleus (ARC) of the hypothalamus by increasing the frequency of action potentials in the hypothalamic POMC neurons by depolarization through a nonspecific cation channel and by reduced inhibition by local orexigenic neuropeptide-Y (NPY) neurons.

Question 6

Which of the following represents the least invasive means to ascertain the extent to which an individual is overweight or obese?&#10;A) BMI&#10;B) glucose tolerance test to measure insulin sensitivity&#10;C) fasting lipid profile&#10;D) fasting plasma glucose concentration&#10;E) urine lipid content

Accepted Answer

BMI (Body Mass Index) is a simple, non-invasive measure that uses height and weight to categorize individuals as underweight, normal weight, overweight, or obese. The BMI is a measure of the relationship between an individual's weight and height. The BMI is calculated by dividing a person's weight in kilograms by the square of their height in meters and is thus completely noninvasive and easy to determine. The medical utility for determining a person's BMI is that this measure describes the body weight relative to height and it, thus, strongly correlates with the total body fat content in adults.

Question 7

You are treating a 38-year-old man whose chief complaint is occasional right upper quadrant pain. Analysis of blood samples shows elevated aspartate transaminase (AST) and alanine transaminase (ALT). History indicates that these same enzymes have shown elevated levels each of the past 3 years during routine blood work in conjunction with his annual physical. His history also indicates reflux esophagitis, hypertension, and hyperlipidemia. You order tests for serologic and biochemical markers for viral hepatitis and autoimmune liver disease and other metabolic liver diseases but these results are negative. The patient has gained 50 lb since the age of 18. He consumes less than 5 alcoholic beverages per week. Which of the following is the most likely diagnosis in this case?

A) cirrhosis
B) nonalcoholic fatty liver disease
C) thyrotoxicosis
D) Type 1 diabetes
E) Type 2 diabetes

Accepted Answer

The patient's elevated liver enzymes, history of weight gain, and minimal alcohol consumption suggest nonalcoholic fatty liver disease (NAFLD), a common liver condition associated with obesity and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world. NAFLD is characterized by fatty infiltration of the liver in the absence of alcohol consumption. One of the most significant contributing factors to the development of NAFLD is insulin resistance in the liver. Additional pathophysiology includes an enhanced state of hepatic oxidative stress and lipid peroxidation, decreased antioxidant defenses, early mitochondrial dysfunction, and iron accumulation.

Question 8

The activity of which of the following adipocyte proteins is associated with increased insulin sensitivity and fatty acid oxidation?&#10;A) adiponectin&#10;B) adipsin&#10;C) leptin&#10;D) resistin&#10;E) vaspin

Accepted Answer

Adiponectin is a protein hormone produced by adipocytes that enhances insulin sensitivity and promotes fatty acid oxidation. The major biological actions of adiponectin are increases in insulin sensitivity and fatty acid oxidation.

Question 9

You are comparing the responses of 2 strains of mice to the effects of a high-fat diet. Your observations show that one strain restricts their intake of food within a short period after accumulating a small gain in weight, whereas the other strain does not. The strain that does not limit their food intake quickly becomes obese. This latter strain of mice would most likely be shown to have a defect in the secretion of which of the following adipokines?

A) adiponectin
B) adipsin
C) leptin
D) resistin
E) vaspin

Accepted Answer

Leptin is an adipokine involved in regulating energy balance by inhibiting hunger. A defect in leptin secretion or signaling can lead to uncontrolled food intake and obesity. Leptin is a peptide whose central function is the regulation of overall body weight by limiting food intake and increasing energy expenditure. Leptin exerts this effect within the brain via activation of the anorexigenic axis (appetite suppression) in the arcuate nucleus (ARC) of the hypothalamus

Question 10

You are carrying out experiments designed to increase energy expenditure as a therapeutic means to treat obesity. You are testing various compounds in experimental animals and find one that appears to satisfy the goals of the experiment in that mice given the compound have a significant increase in thermogenic activity in their adipose tissue. This compound is most likely activating or mimicking the activity of which of the following?

A) adiponectin
B) adipose triglyceride lipase
C) leptin
D) medium-chain acyl-CoA dehydrogenase
E) UCP1

Accepted Answer

UCP1 (Uncoupling Protein 1) is involved in thermogenesis in brown adipose tissue, leading to increased energy expenditure and heat production, which aligns with the observed increase in thermogenic activity in the experiment. Uncoupling protein 1 (UCP1) is a mitochondrial protein of brown adipose tissue (BAT) involved in the process of adaptive thermogenesis. In response to hormonal stimulation of BAT, there is an increase in fatty acid release from triglycerides. The fatty acids enter the mitochondria and activate the mitochondrial uncoupling activity of UCP1. This uncoupling releases the mitochondrial proton gradient as heat

Question 11

You are comparing the responses of 2 strains of mice to the effects of a high-fat diet. Your observations show that although both strains become obese on the diet, one strain has a much higher level of insulin resistance associated with the diet-induced obesity. This latter strain of mice would most likely be shown to have significantly increased levels of secretion of which of the following adipokines?

A) adiponectin
B) adipsin
C) leptin
D) resistin
E) vaspin

Accepted Answer

The answer of You are comparing the responses of 2...

Question 12

Nonalcoholic fatty liver disease (NAFLD) is characterized by fatty infiltration of the liver in the absence of alcohol consumption. This fatty infiltration in the liver is associated with increased insulin resistance. Which of the following represents the most likely target of excess hepatic fatty acids resulting in the insulin resistance associated with NAFLD?

A) glucokinase
B) PFK1
C) PFK2
D) PKA
E) PKC

Accepted Answer

The answer of Nonalcoholic fatty liver disease (NAFLD) is characterized...

Question 13

Which of the following, associated with obesity, is most highly correlated to the development of the metabolic syndrome?&#10;A) elevated serum HDL&#10;B) elevated serum total cholesterol&#10;C) hyperglycemia&#10;D) insulin resistance&#10;E) proteinuria

Accepted Answer

The answer of Which of the following, associated with obesity,...

Question 14

As the level of adipose tissue increases there is a corresponding increase in inflammatory activities associated with this tissue. Which of the following factors is the most significant to the increased proinflammatory activities of expanding fat mass?

A) adiponectin
B) leptin
C) monocyte chemotactic protein-1, MCP-1
D) vascular cell adhesion molecule-1, VCAM-1
E) vascular endothelial cell growth factor, VEGF

Accepted Answer

The answer of As the level of adipose tissue increases...

Question 15

As the level of visceral fat increases there is a concomitant loss of peripheral tissue responses to insulin. Adipose tissue responses to these metabolic changes include a reduced secretion of which of the following adipokines?

A) adiponectin
B) adipsin
C) IL-6
D) leptin
E) resistin

Accepted Answer

The answer of As the level of visceral fat increases...

Deck 45: Adipose Tissue and Obesity: Associated Metabolic Disturbances