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Essential elements of all cells, lipids play important roles in energy production, signalling and as structural components. Despite these critical functions, excessive availability and intracellular accumulation of lipid is now recognised as a major factor contributing to many human diseases, including obesity and diabetes. In the context of these metabolic disorders, ectopic deposition of lipid has been proposed to have deleterious effects of insulin action. While this relationship has been recognised for some time now, there is currently no unifying mechanism to explain how lipids precipitate the development of insulin resistance. This review summarises the evidence linking specific lipid molecules to the induction of insulin resistance, describing some of the current controversies and challenges for future studies in this field.

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Nicotinamide adenine dinucleotide (NAD) plays a vital role in the maintenance of health, and is known to decline with ageing and with metabolic and chronic disease states. Restoration of declining NAD levels—which can be achieved through diet, exercise, and pharmaceutical‐based interventions—has been demonstrated in various organisms to associate with increased longevity and a return to healthy physical function. Our group has previously observed alterations in metabolic processes and in muscle morphology in mice overexpressing the NAD biosynthetic enzyme nicotinamide mononucleotide adenylyl transferase (NMNAT) to target nuclear (NMNAT1) and mitochondrial (NMNAT3) NAD upregulation. In the present investigation, both NMNAT1 and NMNAT3 mice and their respective wildtype littermates were exposed to a six‐week progressive endurance training programme. Endurance capacity, oral glucose tolerance (oGTT), various measures of circulating and tissue lipid and glucose content, and skeletal muscle protein expression were assessed. Despite substantially reduced muscle mass in the NMNAT1Tg/+ group and lower overall performance in the NMNAT3Tg/+ group, the ability to adapt to exercise training was not diminished in either group (improvement above baseline of 147.7 ± 40.1% and 136.6 ± 28.6% for NMNAT1 TG and WT, respectively; and 98.4 ± 36.1% and 72.3 ± 20.5% for NMNAT3 TG and WT, respectively; n = 8–9). Both training and NMNAT1 overexpression were correlated with reduced glucose levels during oGTT, with signs of improved insulin sensitivity evident in the NMNAT1Tg/+ groups; no evidence of improved glucose handling was evident with NMNAT3 overexpression. NMNAT1—but not NMNAT3—overexpression was associated with elevated glycogen storage, with no discernible impact on lipid handling. NMNAT3 overexpression was associated with reduced serum and liver TAG levels in the sedentary but not the trained group. Our results suggest that, despite alterations in glucose and lipid handling, overexpression of NMNAT in the nucleus or the mitochondria does not result in a reduced capacity for adaptation to endurance training. NMNAT overexpression within the nucleus appears to positively impact glucose metabolism; whereas overexpression within the mitochondria appears to alter lipid metabolism in sedentary animals, and these differences diminish with exercise training. Support or Funding Information NHMRC APP1128351

The Arg457Gln missense variant in the CREBRF gene has previously been identified as driving excess body weight in Pacific/Oceanic populations. Intriguingly, Arg457Gln variant carriers also demonstrate paradoxical reductions in diabetes risk, indicating that the gene has a critical role in whole-body metabolism. To study the function of this variant in more detail, we generated mice on an FVB/N background with the Crebrf Arg458Gln variant knocked in to replace the endogenous Crebrf. The whole-body metabolic phenotype was characterized for male and female mice on a regular chow diet or an 8-week high-fat challenge. Regular assessment of body composition found that the Crebrf variant had no influence on total body weight or fat mass at any time point. Glucose tolerance tests demonstrated no obvious genotype effect on glucose homeostasis, with indirect calorimetry measures of whole-body energy expenditure likewise unaffected. Male chow-fed variant carriers displayed a trend towards increased lean mass and significantly reduced sensitivity to insulin administration. Overall, this novel mouse model showed only limited phenotypic effects associated with the Crebrf missense variant. The inability to recapitulate results of human association studies may invite reconsideration of the precise mechanistic link between CREBRF function and the risks of obesity and diabetes in variant allele carriers.

IntroductionIncreasingly person-centered care (PCC) is being recognized as an important aspect of speech-language pathology and audiology (SLP/A) service delivery. This study aimed to (i) identify preferences toward PCC; (ii) determine predictors of these preferences; and (iii) describe the understanding and views of PCC among SLP/A in South Africa.MethodsA mixed-method design was followed utilizing an online survey and four focus group discussions. The survey included demographic questions, the modified Patient-Practitioner Orientation Scale (mPPOS), the Ten-Item-Personality-Inventory (TIPI) and an open-ended question. The focus group discussions included prompting questions which facilitated an open-ended discussion.ResultsA total of 91 practitioners (39.6% speech-language pathologists) completed the online survey, with nine (44.4% audiologists) participating in the focus group discussions. A high preference toward PCC was noted, with a total mean mPPOS score of 4.6 (0.6 SD). Quantile regression analysis revealed four predictors (age, home language, sector, and personality trait openness) associated with PCC preferences. Three main categories emerged from the open-ended question and focus group discussions: (i) Positive experiences with PCC; (ii) restrictions toward PCC, and (iii) PCC exposure.DiscussionPositive (age and personality trait openness) and negative (home language and sector of employment) predictors toward PCC exist among speech-language pathologists and audiologists, with an overall general preference toward PCC. Practitioners experience facilitators and barriers toward implementing PCC including the extent of personal experiences, available resources and tools as well as workplace culture. These aspects require further investigation.

Nicotinamide adenine dinucleotide (NAD) plays a vital role in the maintenance of health and is known to decline with ageing and with metabolic and chronic disease states. Restoration of declining NAD levels—which can be achieved through diet, exercise, and pharmaceutical‐based interventions—has been demonstrated in various organisms to associate with increased longevity and a return to healthy physical function. Our group has previously observed alterations in metabolic processes and in muscle morphology in mice overexpressing the NAD biosynthetic enzyme nicotinamide mononucleotide adenylyl transferase (NMNAT) to target nuclear (NMNAT1) and mitochondrial (NMNAT3) NAD upregulation. In the present investigation, both NMNAT1 and NMNAT3 mice and their respective wildtype littermates were exposed to a six‐week progressive endurance training programme. Endurance capacity, oral glucose tolerance (oGTT), various measures of circulating and tissue lipid and glucose content, and skeletal muscle protein expression were assessed. Despite substantially reduced muscle mass in the NMNAT1Tg/+ group and lower overall performance in the NMNAT3Tg/+ group, the ability to adapt to exercise training was not diminished in either group (improvement above baseline of 147.7 ± 40.1% and 136.6 ± 28.6% for NMNAT1 TG and WT, respectively; and 98.4 ± 36.1% and 72.3 ± 20.5% for NMNAT3 TG and WT, respectively; n = 8‐9). NMNAT1 overexpression was associated with signs of altered glucose handling, including increased storage of glycogen in liver and quadriceps, but little evidence for altered lipid handling was present. NMNAT3 overexpression, by contrast, did not present with any alterations in glucose metabolism or glycogen storage, but did result in reductions in serum, liver, and heart triglycerides within sedentary but not trained animals. Our results suggest that, despite alterations in glucose and lipid handling, overexpression of NMNAT in the nucleus or the mitochondria does not result in a reduced capacity for adaptation to endurance training. NMNAT overexpression within the nucleus appears to positively impact glucose metabolism; whereas overexpression within the mitochondria appears to alter lipid metabolism in sedentary animals, and these differences diminish with exercise training.

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