Honeybee Associative Learning Performance and Metabolic Stress Resilience Are Positively Associated

Background: Social-environmental influences can affect animal cognition and health. Also, human socio-economic status is a covariate factor connecting psychometric test-performance (a measure of cognitive ability), educational achievement, lifetime health, and survival. The complimentary hypothesis, that mechanisms in physiology can explain some covariance between the same traits, is disputed. Possible mechanisms involve metabolic biology affecting integrity and stability of physiological systems during development and ageing. Knowledge of these relationships is incomplete, and underlying processes are challenging to reveal in people. Model animals, however, can provide insights into connections between metabolic biology and physiological stability that may aid efforts to reduce human health and longevity disparities. Results: We document a positive correlation between a measure of associative learning performance and the metabolic stress resilience of honeybees. This relationship is independent of social factors, and may provide basic insights into how central nervous system (CNS) function and metabolic biology can be associated. Controlling for social environment, age, and learning motivation in each bee, we establish that learning in Pavlovian conditioning to an odour is positively correlated with individual survival time in hyperoxia. Hyperoxia induces oxidative metabolic damage, and provides a measure of metabolic stress resistance that is often related to overall lifespan in laboratory animals. The positive relationship between Pavlovian learning ability and stress resilience in the bee is not equally established in other model organisms so far

Gustatory Perception and Fat Body Energy Metabolism Are Jointly Affected by Vitellogenin and Juvenile Hormone in Honey Bees

Honey bees (Apis mellifera) provide a system for studying social and food-related behavior. A caste of workers performs age-related tasks: young bees (nurses) usually feed the brood and other adult bees inside the nest, while older bees (foragers) forage outside for pollen, a protein/lipid source, or nectar, a carbohydrate source. The workers' transition from nursing to foraging and their foraging preferences correlate with differences in gustatory perception, metabolic gene expression, and endocrine physiology including the endocrine factors vitellogenin (Vg) and juvenile hormone (JH). However, the understanding of connections among social behavior, energy metabolism, and endocrine factors is incomplete. We used RNA interference (RNAi) to perturb the gene network of Vg and JH to learn more about these connections through effects on gustation, gene transcripts, and physiology. The RNAi perturbation was achieved by single and double knockdown of the genes ultraspiracle (usp) and vg, which encode a putative JH receptor and Vg, respectively. The double knockdown enhanced gustatory perception and elevated hemolymph glucose, trehalose, and JH. We also observed transcriptional responses in insulin like peptide 1 (ilp1), the adipokinetic hormone receptor (AKHR), and cGMP-dependent protein kinase (PKG, or “foraging gene” Amfor). Our study demonstrates that the Vg–JH regulatory module controls changes in carbohydrate metabolism, but not lipid metabolism, when worker bees shift from nursing to foraging. The module is also placed upstream of ilp1, AKHR, and PKG for the first time. As insulin, adipokinetic hormone (AKH), and PKG pathways influence metabolism and gustation in many animals, we propose that honey bees have conserved pathways in carbohydrate metabolism and conserved connections between energy metabolism and gustatory perception. Thus, perhaps the bee can make general contributions to the understanding of food-related behavior and metabolic disorders

Gene knockdown effect on <i>adipokinetic hormone</i> (<i>AKH</i>) and <i>adipokinetic hormone receptor</i> (<i>AKHR</i>) genes in worker fat body and head.

<p>Relative expression of (A) <i>AKH</i>, (B) <i>AKHR</i> in the fat body, and (C) <i>AKH</i>, (D) <i>AKHR</i> in the brain. While <i>AKH</i> remained unaffected, the double knockdowns of <i>vg</i> and <i>usp</i> had significantly elevated <i>AKHR</i> transcript levels in fat body compared to control. The <i>vg</i> and <i>usp</i> single knockdowns, in contrast, had lower levels of <i>AKHR</i> in the fat body (Mean ± s.e., n = 12, p<0.05).</p

Gene knockdown effect on hemolymph JH titer.

<p>The circulating JH level significantly increased in <i>vg</i> single knockdown bees, as well as in <i>vg</i> and <i>usp</i> double knockdowns (Mean ± s.e., n = 13–16). Double knockdowns (<i>vg-/usp-</i>) had the highest JH titers among all treatment groups (p<0.05).</p

Gene knockdown effect on fat body lipid reserves.

<p>Abdominal lipid content was measured in the same bees that were used to measure hemolymph carbohydrate levels. Lipid content was not affected by the single or double knockdown of <i>vg</i> and <i>usp</i> (Mean ± s.e., n = 18–19, p<0.05).</p

Gene knockdown effect on sucrose responsiveness in 7-day-old bees.

<p>The gustatory responsiveness score (GRS) was measured in the laboratory using the bees' proboscis extension response (PER). High GRS shows that bees responded to low sucrose concentrations, indicating a high gustatory sensitivity. Double knockdown bees (<i>vg-/usp-</i>) showed significantly increased gustatory responsiveness (Mean ± s.e., n = 33–65, p<0.05).</p

Gene knockdown effect on metabolically associated genes in the fat body.

<p>Relative expression of (A) <i>Insulin-like peptide 1</i> (<i>ilp1</i>), (B) <i>Insulin-like peptide 2</i> (<i>ilp2</i>), (C) <i>cGMP-dependent protein kinase</i> (<i>PKG</i>) and (D) <i>Juvenile hormone esterase</i> (<i>JHE</i>). The double knockdown of <i>vg</i> and <i>usp</i> resulted in reduced <i>ilp1</i> and <i>PKG</i> transcripts levels (Mean ± s.e., n = 16, p<0.05).</p

The Association Between Kidney Disease and Diabetes Remission in Bariatric Surgery Patients With Type 2 Diabetes

Rationale & objective: The association between bariatric surgery, type 2 diabetes, and chronic kidney disease (CKD) is poorly understood. We studied whether remission of type 2 diabetes induced by bariatric surgery influences markers of kidney disease, if CKD is associated with remission of diabetes after bariatric surgery, and if baseline levels of gut hormones and peptides modify these associations. Study design: Prospective observational study. Study participants: 737 bariatric surgery patients with type 2 diabetes who participated in a multicenter cohort study for up to 5 years. Predictors: Demographics, blood pressure, medications, type of bariatric surgery, anthropometrics, markers of kidney disease, and circulating levels of gut hormones and peptides. Outcomes: Estimated glomerular filtration rate (eGFR), urinary albumin excretion, prognostic risk for CKD, and remission of diabetes. Analytical approach: Linear mixed models for eGFR; generalized linear mixed models with logit link for albuminuria, prognostic risk for CKD, and diabetes remission. Results: Remission of diabetes at 5 years post-bariatric surgery was not independently associated with eGFR but was associated with lower risk for moderate/severe increase in albuminuria (risk ratio, 0.66; 95% CI, 0.48-0.90) and stabilization in prognostic risk for CKD. These findings were modified by baseline ghrelin level. Lower preoperative eGFR and greater prognostic risk for CKD were independently associated with reduced likelihood of diabetes remission. The association with preoperative GFR was modified by C-peptide level. Higher baseline circulating ghrelin level was independently associated with a lower prognostic risk for CKD. Limitations: A minority of participants had baseline CKD; lack of comparison group; no information on duration of diabetes, other clinical end points, or kidney biopsy results. Conclusions: Remission of type 2 diabetes 5 years after bariatric surgery was associated with improvements in albuminuria and stabilized prognostic risk for CKD, but not with eGFR. Lower kidney function and greater prognostic risk at the time of bariatric surgery was linked to a lower likelihood of diabetes remission. These results highlight the need to identify the mechanisms through which bariatric surgery may delay the long-term progression of CKD in type 2 diabetes. Keywords: C-peptide; CKD risk; Obesity; Roux-en-Y gastric bypass (RYGB); albuminuria; bariatric surgery; chronic kidney disease (CKD); diabetes remission; estimated glomerular filtration rate (eGFR); ghrelin; gut peptides; insulin; laparoscopic adjustable gastric banding (LAGB); modifiable risk factor; type 2 diabetes mellitus (T2DM); urinary albumin-creatinine ratio (UACR); weight loss