Flavonoids are dietary compounds with potential anti-diabetes activities. Many flavonoids have poor bioavailability and thus low circulating concentrations. Unabsorbed flavonoids are metabolized by the gut microbiota to smaller metabolites, which are more bioavailable than their precursors. The activities of these metabolites may be partly responsible for associations between flavonoids and health. However, these activities remain poorly understood. We investigated bioactivities of flavonoid microbial metabolites [hippuric acid (HA), homovanillic acid (HVA), and 5-phenylvaleric acid (5PVA)] in primary skeletal muscle and β-cells compared to a native flavonoid ([(−)-epicatechin, EC]. In muscle, EC was the most potent stimulator of glucose oxidation, while 5PVA and HA simulated glucose metabolism at 25 μM, and all compounds preserved mitochondrial function after insult. However, EC and the metabolites did not uncouple mitochonndrial respiration, with the exception of 5PVA at10 μM. In β-cells, all metabolites more potently enhanced glucose-stimulated insulin secretion (GSIS) compared to EC. Unlike EC, the metabolites appear to enhance GSIS without enhancing β-cell mitochondrial respiration or increasing expression of mitochondrial electron transport chain components, and with varying effects on β-cell insulin content. The present results demonstrate the activities of flavonoid microbial metabolites for preservation of β-cell function and glucose utilization. Additionally, our data suggest that metabolites and native compounds may act by distinct mechanisms, suggesting complementary and synergistic activities in vivo which warrant further investigation. This raises the intriguing prospect that bioavailability of native dietary flavonoids may not be as critical of a limiting factor to bioactivity as previously thought.

Approximately 366 million people worldwide have been diagnosed with type-2 diabetes (T2D). Chronic insulin resistance, decreased functional β-cell mass, and elevated blood glucose are defining characteristics of T2D. Great advances have been made in understanding the pathogenesis of T2D with respect to the effects of dietary macronutrient composition and energy intake on β-cell physiology and glucose homeostasis. It has been further established that obesity is a leading pathogenic factor for developing insulin resistance. However, insulin resistance may not progress to T2D unless β-cells are unable to secret an adequate amount of insulin to compensate for decreased insulin sensitivity. Therefore, pancreatic β-cell dysfunction plays an important role in the development of overt diabetes. This paper reviews recent research findings on the effects of several micronutrients (zinc, vitamin D, iron, vitamin A), leucine, and the phytochemical, genistein on pancreatic β-cell physiology with emphasis on their effects on insulin secretion, specifically in the context of T2D.

Impaired fertility during periods of heat stress is the culmination of numerous physiological responses to heat stress, ranging from reduced estrus expression and altered follicular function to early embryonic death. Furthermore, heat-stressed dairy cattle exhibit a unique metabolic status that likely contributes to the observed reduction in fertility. An understanding of this unique physiological response can be used as a basis for improving cow management strategies, thereby reducing the negative effects of heat stress on reproduction. Potential opportunities for improving the management of dairy cattle during heat stress vary greatly and include feed additives, targeted cooling, genetic selection, embryo transfer and, potentially, crossbreeding. Previous studies indicate that dietary interventions such as melatonin and chromium supplementation could alleviate some of the detrimental effects of heat stress on fertility, and that factors involved in the methionine cycle would likely do the same. These supplements, particularly chromium, may improve reproductive performance during heat stress by alleviating insulinmediated damage to the follicle and its enclosed cumulus-oocyte complex. Beyond feed additives, some of the simplest, yet most effective strategies involve altering the timing of feeding and cooling to take advantage of comparatively low nighttime temperatures. Likewise, expansion of cooling systems to include breeding-age heifers and dry cows has significant benefits for dams and their offspring. More complicated but promising strategies involve the calculation of breeding values for thermotolerance, the identification of genomic markers for heat tolerance, and the development of beddingbased conductive cooling systems. Unfortunately, no single approach can completely rescue the fertility of lactating dairy cows during heat stress. That said, region-appropriate combinations of strategies can improve reproductive measures to reasonable levels.

Heat stress (HS) diminishes animal production, reducing muscle growth and increasing adiposity, especially in swine. Excess heat creates a metabolic phenotype with limited lipid oxidation that relies on aerobic and anaerobic glycolysis as a predominant means of energy production, potentially reducing metabolic rate. To evaluate the effects of HS on substrate utilization and energy expenditure, crossbred barrows (15.2 ± 2.4 kg) were acclimatized for 5 days (22 °C), then treated with 5 days of TN (thermal neutral, 22 °C, n = 8) or HS (35 °C, n = 8). Pigs were fed ad libitum and monitored for respiratory rate (RR) and rectal temperature. Daily energy expenditure (DEE) and respiratory exchange ratio (RER, CO2:O2) were evaluated fasted in an enclosed chamber through indirect calorimetry. Muscle biopsies were obtained from the longissimus dorsi pre/post. HS increased temperature (39.2 ± 0.1 vs. 39.6 ± 0.1 °C, p < 0.01) and RER (0.91 ± 0.02 vs. 1.02 ± 0.02 VCO2:VO2, p < 0.01), but decreased DEE/BW (68.8 ± 1.7 vs. 49.7 ± 4.8 kcal/day/kg, p < 0.01) relative to TN. Weight gain (p = 0.80) and feed intake (p = 0.84) did not differ between HS and TN groups. HS decreased muscle metabolic flexibility (~33%, p = 0.01), but increased leucine oxidation (~35%, p = 0.02) compared to baseline values. These data demonstrate that HS disrupts substrate regulation and energy expenditure in growing pigs.

Substantial economic losses in animal agriculture result from animals experiencing heat stress (HS). Pigs are especially susceptible to HS, resulting in reductions in growth, altered body composition, and compromised substrate metabolism. In this study, an artificial high-intensity sweetener and capsaicin (CAPS-SUC; Pancosma, Switzerland) were supplemented in combination to mitigate the adverse effects of HS on pig performance. Forty cross-bred barrows (16.2 ± 6 kg) were assigned to one of five treatments: thermal neutral controls (TN) (22 ± 1.2 °C; 38%–73% relative humidity) with ad libitum feed, HS conditions with ad libitum feed with (HS+) or without (HS−) supplementation, and pair-fed to HS with (PF+) or without supplementation (PF−). Pigs in heat-stressed treatments were exposed to a cyclical environmental temperature of 12 h at 35 ± 1.2 °C with 27%–45% relative humidity and 12 h at 30 ± 1.1 °C with 24%–35% relative humidity for 21 d. Supplementation (0.1 g/kg feed) began 7 d before and persisted through the duration of environmental or dietary treatments (HS/PF), which lasted for 21 d. Rectal temperatures and respiration rates (RR; breaths/minute) were recorded thrice daily, and feed intake (FI) was recorded daily. Before the start and at the termination of environmental treatments (HS/PF), a muscle biopsy of the longissimus dorsi was taken for metabolic analyses. Blood samples were collected weekly, and animals were weighed every 3 d during treatment. Core temperature (TN 39.2 ± 0.02 °C, HS− 39.6 ± 0.02 °C, and HS+ 39.6 ± 0.02 °C, P &lt; 0.001) and RR (P &lt; 0.001) were increased in both HS− and HS+ groups, but no difference was detected between HS− and HS+. PF− pigs exhibited reduced core temperature (39.1 ± 0.02 °C, P &lt; 0.001), which was restored in PF+ pigs (39.3 ± 0.02 °C) to match TN. Weight gain and feed efficiency were reduced in PF− pigs (P &lt; 0.05) but not in the PF+ or the HS− or HS+ groups. Metabolic flexibility was decreased in the HS− group (−48.4%, P &lt; 0.05) but maintained in the HS+ group. CAPS-SUC did not influence core temperature or weight gain in HS pigs but did restore core temperature, weight gain, and feed efficiency in supplemented PF pigs. In addition, supplementation restored metabolic flexibility during HS and improved weight gain and feed efficiency during PF, highlighting CAPS-SUC’s therapeutic metabolic effects.