Lit Metabolic, Nutrition

Question 1

1) a) What is spexin? b) Where is it expressed & detectable?
3) Spexin is negatively correlated with …. (6 variables) and positively correlated with ….. (1 variable) in dogs.

Answer 1

Kolodziejski JVIM 2021
1) a) Peptide hormone that regulates BW, adipose tissue metabolism & food intake. Potential marker for obesity.
b) Spexin mRNA detectable in adipose tissue, liver & pancreas. Expressed in adipose & liver but not pancreas.
2) Negative correlation - BCS, serum insulin concentration, leptin, total cholesterol, NEFA, fructosamine. Positive correlation - adiponectin.

Question 2

The following dietary exposure factors in puppyhood were associated with …. (higher or lower) risk of atopic dermatitis in adulthood in Finnish dogs?
a) Fruits
b) Raw foods
c) Fish oil supplements
d) Mixed oils
e) Heat processed foods

Answer 2

Hemida JVIM 2021
a) Higher, b) lower, c) lower, d) higher, e) higher

Question 3

What differences in serum TG, chol & lipoprotein profiles were observed between dogs with pancreatitis vs healthy dogs?

Answer 3

Xenoulis JVIM 2020
Mild increases in dogs with hyperTG (18%, sig diff vs healthy dogs 7.5%) and/or hyperCHOL (24%, not sig diff vs healthy dogs).
Pancreatitis dogs had higher LDL fractions, lower TG-rich lipoprotein, & lower HDL fractions.

Question 4

The 3 major uremic toxins produced by colonic bacteria which are associated with disease progression in CKD cats are: ………….

When comparing faecal short-chain fatty acids (SCFA) between CKD & healthy geriatric cats, ……… concentrations were higher in CKD cats especially in …… stages.

Faecal branched-chain fatty acid concentrations correlated with …….(uremic toxin), and were higher in CKD cats with ……….., indicating ……………

Answer 4

Summers JVIM 2019
Indoxyl sulfate (IS), p-cresol sulfate (pCS), trimethylamine-N-oxide (TNO)

Late stages (IRIS 3-4)

pCS; muscle wastage; protein malassimilation

Question 5

What were the differences in faecal microbiota composition between puppies <5-6 weeks old & adult dogs?

Answer 5

Blake JVIM 2020
Puppies up to 5-6 weeks of age had increased Dysbiosis Index, increased abundance of C. difficile, and decreased secondary bile acid concentrations associated with decreased abundance of C. hiranonis cf adult dogs.
(Secondary BA likely have regulatory role on clostridial spp. in dogs)

Question 6

Causes of hypercobalaminemia in dogs & cats?

Answer 6

Kather Vet J 2020
Dogs - overall 3% incidence of high B12. DDx chronic GI signs (48%), hypoA (uncommon)
Cats - chronic enteropathy (65%), acute/chronic pancreatitis (24%), cholangiohepatopathy, gastric lymphoma (6%), hyperT (3%).

Question 7

What risk factors were identified in 2 distinct outbreaks of acquired idiopathic megaO in dogs in Latvia & Australia?

Differences in clinical presentation?

Answer 7

Hurley JAVMA 2021
Large breed male dogs (>25kg). 2 brands of commercial adult dog biscuits (no specific toxin identified).

Latvian population - mild to severe peripheral polyneuropathies - laryngeal paralysis, dysphonia, weakness. Histo findings consistent with distal axonopathy.
Aus population - peripheral polyneuropathies not identified. Histo showed local disruption to innervation of oesophagus & pharynx.

Question 8

What are the clinical consequences of high dietary phosphate intake in cats?

Answer 8

JVIM 2019
High P (in particular inorganic P) & low Ca:P ratios have been associated with renal damage in cats.

Question 9

What inflammatory marker was increased in Mini Schnauzers with hyperlipidemia? Did this respond to diet?

Answer 9

Heilmann JVIM 2019
Calprotectin - consistent with subclinical low-grade inflammation in dogs with HL. Calprotectin positively correlated to combined HL & hyperTG but not hyperCHOL alone.

Lipid status improved within 3.5-6.5mths of ultra-low fat diet, but calprotectin did not.

Question 10

Median % change in thoracic dimension & lung area changes are affected by …… in healthy dogs?

Answer 10

Chan JVIM 2017
Body weight.

Fluoroscopy used to measure lung area changes during respiration - must be corrected for BW.

Question 11

What B vitamin derangements are common in Greyhounds, and how prevalent?

What secondary metabolite increases as a result? What are the potential systemic complications of increase in this secondary metabolite?

Answer 11

Heilmann JVIM 2017

Hypofolatemia (B9) - 41% Greyhounds. Often concurrent with hypocobalaminaemia (49% of hypoFOL dogs).

Associated with increases in homocysteine (hyperhomocysteinemia) - as B9 & B12 are required as cofactors for its metabolism.

People - hyperHOMO associated with chronic GI disease, CVS disease, thrombosis, neurodegenerative disease.

HyperHOMO observed in 100% healthy Greyhounds, 70% dogs with chronic D+, 75% with thrombosis.

Question 12

In which of the following were canine breed differences in plasma/serum concentrations observed: endothelin-1, cortisol & renin? Which breeds had the highest concentrations of each hormone??

Answer 12

Höglund JVIM 2016

All 3.
ET-1: highest in Newfoundlands
Renin: highest in Dachshunds
Cortisol: highest in Finnish Laphunds

Question 13

Where is the Vitamin D receptor expressed in tissues? Is this affected by chronic enteropathy?

Answer 13

Cartwright JVIM 2018
Highest - kidney, duodenum, ileum, spleen, skin.
Weak - colon, heart, LN, liver, lung, ovary.
Absent - gastric & testicular.
No reduction in expression in CE dogs (compared duodenal VDR).

Question 14

What is the association between calcidiol & iCa in dogs with cancer, and compared to healthy dogs?

What is role of the CYP24A1 gene in vitamin D metabolism?

Answer 14

Weidner JVIM 2017

Dogs with cancer had INCREASED calcidiol concentrations with higher iCa - suggesting altered Vit D metabolism.
In contrast healthy dogs had DECREASED calcidiol concentrations with higher iCa.

CYP24A1 gene encodes production of 25-hydroxyvitamin D-24-hydroxylase enzyme which converts 25(OH)D (calcidiol) to 24,25(OH)2D (inactive form) - regulates amt of active vit D in circulation.

Question 15

What % of Mini Schnauzers with primary hyperTG were proteinuric?
Which biochemical changes were significantly associated with proteinuria in these dogs?

Answer 15

Smith JVIM 2017

56% of dogs in the study had primary hyperTG, of which 44% were proteinuric.

Increased serum albumin (NOT hypoalbuminemia), increased ALKP, increased CHOL.
NOT azotemia.
Azotemia & hypoalb not documented on longer FU period of 18mths in this study.
Also no increased risk of hypertension, decreased antithrombin III activity, or cardiac disease noted in these dogs (vs people).

Question 16

What was the effect of feeding a prescription low-fat diet (18.6g fat/1000kcal) on the lipid profiles of Mini Schnauzers with primary hypertriglyceridemia?

Answer 16

Xenoulis JVIM 2020

Diet was effective in reducing serum TG & CHOL concentrations, and correcting lipoprotein profiles (50% of hyperlipidemic dogs had normalisation of lipoprotein profiles after diet).

Question 17

Bezafibrate
- MOA
- Indications
- Efficacy for the indication listed above?
- What biochemical parameter improved in line with therapeutic response to drug?

Answer 17

De Marco JVIM 2017

MOA: Peroxisome proliferator-activated receptor-alpha (PPAR-a) agonist.
Increases LPL activity –> increases FFA uptake into hepatocytes, decreases hepatic triglyceride & VLDL production in the liver. Increases GB exertion of hepatic CHO, increases HDL production.

Treatment of hyperTG in dogs. (Note effect on CHOL as well even though not labelled for hyperCHOL).
Normalised TG in 91% of hyperlipidemic dogs, and cholesterol in 66% after 30 days of tx.
(Greater decrease in TG in primary hyperLP dogs vs secondary).

ALT elevation - this decreased significantly after 30 days of treatment.

Question 18

What is the proposed advantage of using Tricor (micronised nanocrystal formulation of fenofibrate) over generic formulations?
What was the efficacy of this formulation in treatment of dogs with primary & secondary hyperlipidemia?

Answer 18

Munro JVIM 2021

Fenofibrate is a highly lipophilic drug with poor water solubility & oral bioavailability, needs to be given with food to maximise bioavailability. Tricor allows for more predictable absorption, effective treatment at lower & more precise doses + reduced risk of adverse reactions cf generic fenofibrate.

Over 3-7 weeks, TriCor normalised TG in 100% dogs & decreased serum CHOL in 90% dogs. Also sig reduced ALKP activity. Overall effective & well tolerated. (AE - quiet demeanour, firm stools noted in 1/10 dogs).

Question 19

What amino acid derangements can be observed in PLN dogs?

Answer 19

Parker JVIM 2019

Significantly lower:
- Total sum of AAs (essential + non-essential).
- Concentrations of leucine, threonine, histidine, glycine, proline, asparagine, tyrosine, o-hydroxyproline & serine.

Question 20

What conditions apart from acute pancreatitis are associated with hyperlipasemia in dogs?
What clinical factors were predictive of hyperlipasemia?
What is the clinical significance of hyperlipasemia?

Answer 20

Prümmer JVIM 2020
Renal & immune-mediated diseases more common in this study; also endocrine & upper airway obstruction.
Of dogs with hyperlipasemia, 17% had AP.
Predictors - hemodialysis, increased plasma BIL & crea, decreased Hct.
DGGR-hyperlipasemia at admission and/or during hospitalisation associated with longer hosp & higher mortality.

Question 21

What is the POMC gene in Labradors associated with?

Answer 21

Davison JVIM 2017
Associated with obesity and food motivation. No association found with diabetes

Soder JVIM 2016

Question 22

What is a deletion in the pro-opiomelanocortin (POMC) gene in Labradors associated with?

Answer 22

Davison JVIM 2017
Associated with obesity and food motivation. No association found with susceptibility to DM.
Study developed PCR-based test to detect gene deletion.

Question 23

What differences in metabolic responses were observed after feeding a high-fat mixed meal in lean vs overweight dogs?

Answer 23

Söder JVIM 2016
Overall similar post-prandial response as people (increased insulin & glucagon; TG & glucose).
Overweight dogs had higher postprandial triglyceride response & fasting cortisol/creatinine ratio&raquo_space;> possible early signs of metabolic imbalance.

Question 24

What is the risk of death in overweight dogs compared to neutered pet dogs with normal BW?

Answer 24

Salt JVIM 2019
HR 1.35-2.86 (varied by breed). Greatest difference in lifespan in Yorkies (13yrs vs 16 yrs), least in GSDs (both 12yrs).

Question 25

Compared to ideal weight controls, obese dogs had the following metabolic derangements:
1. ……. insulin/glucose ratio, indicating ……
2. …….. characterised by ….. cholesterol, TG & HDLP concentrations
3. ….. serum adiponectin concentrations
4. Increased inflammatory markers including ….. (name 2)
5. ……blood pressure

Answer 25

Tropf JVIM 2017
1. Increased; insulin resistance
2. Dyslipidemia; increased
3. Decreased
4. IL-8
5. Keratinocyte-derived chemokine-like inflammatory cytokines
6. No sig diff (study still concluded possible systemic hypertension in this group)

Concluded that above derangements may alter cardiac function (based on echo findings).

Question 26

Why are cats with ileal disease predisposed to taurine deficiency? Were whole blood taurine concentrations lower in cats with intestinal disease, and were there differences depending on which intestinal segment(s) was/were involved?

Answer 26

Kathrani JVIM 2017
Taurine = essential AA in cats as lack metabolic pathways to synthesize it from precursors methionine & cysteine. Also cats conjugate bile acids solely with taurine (vs glycine > taurine in dogs) which are absorbed from the terminal ileum, so ileal disease impairs absorption of taurine-conjugated BAs.

Whole blood taurine concentrations were WRI for cats with GI disease, but were sig LOWER in cats with LI signs cf SI/mixed intestinal signs. Alplied to both cats with CIE & intestinal neoplasia.

Question 27

Based on a systemic review, were there differences in short vs long term outcome between feeding an intestinal diet (with proteins from various sources) vs hydrolyzed soy protein diet in dogs with SI D+? What about in cats?

Answer 27

Makielski JVIM 2019
Dogs - both diets had similar short term (3mths) clinical response of 88%, but sig higher clinical remission rates in dogs fed hydrolyzed diets (13/14 vs 1/6 with intestinal). Strong evidence
Cats - no sig diff noted, but studies may have been underpowered

Overall review recommended feeding elimination diet to maintain clinical remission in dogs & cats, but not known if novel intact vs hydrolyzed protein diets are more effective.

Question 28

What is the causal gene mutation for Musladin-Lueke Syndrome and which dog breed is affected? What is a classic clinical sign?

Answer 28

Packer JVIM 2017
Connective tissue disorder.
ADAMTSL2 gene mutation, autosomal recessive.
Beagles.
Gait abnormalities (walking on tiptoes with all 4 limbs in rigid extension like a ballerina)

Question 29

What is the causal gene mutation for Musladin-Lueke Syndrome and which dog breed is affected? What is a classic clinical sign?

Answer 29

Packer JVIM 2017
Connective tissue disorder.
ADAMTSL2 gene mutation, autosomal recessive.
Beagles.
Gait abnormalities (walking on tiptoes with all 4 limbs in rigid extension like a ballerina)

Question 30

What lipid derangements were associated with non-survival in ICU hospitalised dogs?

Answer 30

Viall JAVMA 2019
Hypocholesterolemia & hypertriglyceridemia (alone or combo) at presentation.