Logan K. Townsend

Subcutaneous inguinal white adipose tissue is responsive to, but dispensable for, the metabolic health benefits of exercise

Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT)-like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise. To test this, male C57BL/6 mice were provided access to voluntary wheel running (VWR) or remained as a cage control (SED) for 11 nights after iWAT removal via lipectomy (LIPX) or SHAM surgery. We found that SHAM and LIPX mice with access to VWR ran similar distances and had comparable reductions in body mass, increased food intake, and increased respiratory exchange ratio (RER). Further, VWR improved indexes of glucose homeostasis and insulin tolerance in both SHAM and LIPX mice. The lack of effect of LIPX in the response to VWR was not explained by compensatory increases in markers of mitochondrial biogenesis and thermogenesis in skeletal muscle, epididymal white adipose tissue, or interscapular brown adipose tissue. Together, these data demonstrate that mice with and without iWAT have comparable adaptations to VWR, suggesting that iWAT may be dispensable for the metabolic health benefits of exercise.

Obesity exacerbates the acute metabolic side effects of olanzapine

Olanzapine is a second-generation antipsychotic used in the management of schizophrenia and various off-label conditions. The acute metabolic responses of olanzapine recapitulate many of the side effects associated with obesity. Obesity rates are high in the schizophrenic population, but it is unknown whether pre-existing obesity-associated metabolic dysfunction augments the acute side effects of olanzapine. To address this question, we compared the responses to olanzapine in lean and high-fat diet-induced (HFD) obese mice. Four weeks of HFD (60%kcal from fat) led to obese, hyperglycemic, and insulin resistant mice. Olanzapine-induced hyperglycemia and systemic insulin resistance were exacerbated in HFD-induced obese mice. Olanzapine also profoundly inhibited insulin signalling in skeletal muscle and liver, which appears to be exacerbated by obesity. The greater olanzapine-induced hyperglycemia may also result from increased hepatic glucose output in obese mice as pyruvate challenge led to significantly higher blood glucose concentrations, with associated increases in hepatic content of gluconeogenic enzymes. Olanzapine also suppressed RER while acutely increasing oxygen consumption in obese mice. A single olanzapine treatment reduced physical activity for up to 24h, regardless of obesity. Considering obesity is very common in the schizophrenic population, these data suggest that previous research may be under-estimating the severity of olanzapines acute side effects.

Cycling our way to fit fat

Adipose tissue is increasingly being recognized as a key regulator of whole body carbohydrate and lipid metabolism. In conditions of obesity and insulin resistance mitochondrial content in this tissue is reduced, while treatment with insulin sensitizing drugs such as thiazolidinediones (TZDs) increase mitochondrial content. It has been known for decades that exercise increases mitochondrial content in skeletal muscle and now several laboratories have shown similar effects in adipose tissue. To date the specific mechanisms mediating this effect have not been fully identified. In this review we highlight recent work suggesting that increases in lipolysis and subsequently fatty acid re‐esterification trigger the activation of 5 AMP‐activated protein kinase (AMP) activated protein kinase and ultimately the induction of mitochondrial biogenesis. It is our current view that this pathway could be a unifying mechanism linking numerous systemic factors (catecholamines, interleukin‐6, meteorin‐like) to induction of mitochondrial biogenesis following exercise.

Potential involvement of lactate and interleukin-6 in the appetite-regulatory hormonal response to an acute exercise bout

This study examines the involvement of two potential mechanisms (lactate and IL-6) that may explain the intensity-dependent effects of acute exercise on appetite-related parameters. Our findings support a clear intensity-dependent paradigm for appetite-regulation following exercise, as highlighted by the change in acylated ghrelin and the suppression of appetite and energy intake after vigorous exercise (continuous and intermittent). Further, our findings extend previous work in animal/cell models by providing evidence for the potential role of lactate and IL-6 in mediating changes in appetite-related parameters following exercise in humans.

Looking on the “brite” side exercise-induced browning of white adipose tissue

The need for effective and convenient ways of combatting obesity has created great interest in brown adipose tissue (BAT). However, because adult humans have relatively little amounts of BAT, the possibility of browning white adipose tissue (WAT), i.e., switching the metabolism of WAT from an energy storing to energy burning organ, has gained considerable attention. Exercise has countless health benefits, and has consistently been shown to cause browning in rodent white adipose tissue. The purpose of this review is to provide an overview of recent studies examining the effects of exercise and other interventions on the browning of white adipose tissue. The role of various endocrine factors, including catecholamines, interleukin-6, irisin, and meteorin-like in addition to local re-esterification-mediated mechanisms in inducing the browning of WAT will be discussed. The physiological importance of browning will be discussed, as will discrepancies in the literature between human and rodent studies.

Dairy Attenuates Weight Gain to a Similar Extent as Exercise in Rats Fed a High-Fat, High-Sugar Diet

To compare the individual and combined effects of dairy and endurance exercise training in reducing weight gain and adiposity in a rodent model of diet‐induced obesity.

Prior exercise training improves cold tolerance independent of indices associated with non-shivering thermogenesis

Mammals defend against cold‐induced reductions in body temperature through both shivering and non‐shivering thermogenesis. The activation of non‐shivering thermogenesis is primarily driven by uncoupling protein‐1 in brown adipose tissue and to a lesser degree by the browning of white adipose tissue. Endurance exercise has also been shown to increase markers of white adipose tissue browning. This study aimed to determine whether prior exercise training would alter the response to a cold challenge and if this would be associated with differences in indices of non‐shivering thermogenesis. It is shown that exercise training protects against cold‐induced weight loss by increasing food intake. Exercise‐trained mice were better able to maintain their core temperature, independent of differences in markers of non‐shivering thermogenesis.

AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis

Olanzapine (OLZ) is an antipsychotic drug used in the treatment of schizophrenia. Although effective in reducing psychoses, OLZ causes acute increases in blood glucose. The acute effects of OLZ on hyperglycemia are likely caused by reductions in insulin secretion, insulin resistance, and increased hepatic glucose production. 5AMP-activated protein kinase (AMPK) is an energy sensor activated during exercise that can increase insulin sensitivity and insulin-independent glucose uptake in muscle. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) is a pharmacologic agent that, among other effects, can activate AMPK in vivo. Conversely, hypothalamic activation of AMPK has been suggested to mediate the hyperglycemic effects of OLZ. The purpose of this investigation was to determine whether cotreatment with AICAR could prevent acute OLZ-induced hyperglycemia in lean and obese C57BL6/J mice. OLZ (5 mg/kg, i.p.) caused rapid increases in blood glucose, a blunted insulin response, and pyruvate intolerance, all of which were prevented with AICAR cotreatment in both lean and obese mice. AICAR did not affect OLZ-induced changes in whole-body substrate oxidation or energy expenditure. Peripheral injection of AICAR, but not OLZ, activated AMPK signaling in the hypothalamus. The results of the current study provide evidence that AICAR prevents OLZ-induced hyperglycemia, despite increasing hypothalamic AMPK signaling. These protective effects were associated with the preservation of whole-body insulin action and reductions in markers of liver glucose production.

Using PLIN proteins to explain the athlete's paradox

Modern humans over-consume calories so much that adipose tissue can no longer keep up with storage requirements, forcing other tissues, like skeletal muscle, to compensate by storing more lipids (IMTG). n nThis article is protected by copyright. All rights reserved