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Physiol Behav. 2017 Jul 1;176:139-148. doi: 10.1016/j.physbeh.2017.03.040. Epub 2017 Mar 28.

Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet.

Author information

1
Minnesota Obesity Prevention Training Program, University of Minnesota, United States; Geriatric Research and Clinical Center, Minneapolis VA Health Care System, United States. Electronic address: pgrebens@umn.edu.
2
Medical Devices Center, University of Minnesota, United States.
3
Food Science and Nutrition, University of Minnesota, United States.
4
Department of Medicine, University of Minnesota, United States; Minnesota Obesity Center, University of Minnesota, United States; Department of Medicine, Minneapolis VA Health Care System, United States.
5
Geriatric Research and Clinical Center, Minneapolis VA Health Care System, United States; Minnesota Obesity Center, University of Minnesota, United States; Department of Integrative Biology and Physiology, University of Minnesota, United States.

Abstract

Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). We hypothesized that HFD decreases SPA and NEAT, and that DREADD-mediated activation of orexin neuron signaling would abolish this decrease and produce an increase in NEAT instead. To test these ideas, we characterized behaviors to determine the extent to which access to a high-fat diet (HFD) influences the proportion and probability of engaging in food intake and activity. We then measured NEAT following access to HFD and following a DREADD intervention targeting orexin neurons. Two cohorts of orexin-cre male mice were injected with an excitatory DREADD virus into the caudal hypothalamus, where orexin neurons are concentrated. Mice were then housed in continuous metabolic phenotyping cages (Sable Promethion). Food intake, indirect calorimetry, and SPA were automatically measured every second. For cohort 1 (n=8), animals were given access to chow, then switched to HFD. For cohort 2 (n=4/group), half of the animals were given access to HFD, the other access to chow. Then, among animals on HFD, orexin neurons were activated following injections of clozapine n-oxide (CNO). Mice on HFD spent significantly less time eating (p<0.01) and more time inactive compared to mice on chow (p<0.01). Following a meal, mice on HFD were significantly more likely to engage in periods of inactivity compared to those on chow (p<0.05). NEAT was decreased in animals on HFD, and was increased to the NEAT level of control animals following activation of orexin neurons with DREADDs. Food intake (kilocalories) was not significantly different between mice on chow and HFD, yet mice on chow expended more energy per unit of SPA, relative to that in mice consuming HFD. These results suggest that HFD consumption reduces SPA and NEAT, and increases inactivity following a meal. Together, the data suggest a change in the efficiency of energy expenditure based upon diet, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.

KEYWORDS:

Designer receptors exclusively activated by designer drugs (DREADDs); High-fat diet; Non-exercise activity thermogenesis (NEAT); Orexin; Spontaneous physical activity (SPA)

PMID:
28363838
PMCID:
PMC5510739
DOI:
10.1016/j.physbeh.2017.03.040
[Indexed for MEDLINE]
Free PMC Article

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