Cannabinoid-1 receptor activation modulates lipid mobilization and adipogenesis in the adipose tissue of dairy cows.

Amplified adipose tissue (AT) lipolysis and suppressed lipogenesis characterize the periparturient period of dairy cows. The intensity of lipolysis recedes with the progression of lactation; however, when lipolysis is excessive and prolonged, disease risk is exacerbated and productivity compromised. Interventions that minimize lipolysis while maintaining adequate supply of energy and enhancing lipogenesis may improve periparturient cows' health and lactation performance. Cannabinoid-1 receptor (CB1R) activation in rodent AT enhances the lipogenic and adipogenic capacity of adipocytes, yet the effects in dairy cow AT remain unknown. Using a synthetic CB1R agonist and an antagonist, we determined the effects of CB1R stimulation on lipolysis, lipogenesis, and adipogenesis in the AT of dairy cows. Adipose tissue explants were collected from healthy, nonlactating and nongestating (NLNG; n = 6) or periparturient (n = 12) cows at 1 wk before parturition and at 2 and 3 wk postpartum (PP1 and PP2, respectively). Explants were treated with the ß-adrenergic agonist isoproterenol (1 µM) in the presence of the CB1R agonist arachidonyl-2'-chloroethylamide (ACEA) ± the CB1R antagonist rimonabant (RIM). Lipolysis was quantified based on glycerol release. We found that ACEA reduced lipolysis in NLNG cows; however, it did not exhibit a direct effect on AT lipolysis in periparturient cows. Inhibition of CB1R with RIM in postpartum cow AT did not alter lipolysis. To evaluate adipogenesis and lipogenesis, preadipocytes isolated from NLNG cows' AT were induced to differentiate in the presence or absence of ACEA ± RIM for 4 and 12 d. Live cell imaging, lipid accumulation, and expressions of key adipogenic and lipogenic markers were assessed. Preadipocytes treated with ACEA had higher adipogenesis, whereas ACEA+RIM reduced it. Adipocytes treated with ACEA and RIM for 12 d exhibited enhanced lipogenesis compared with untreated cells (control). Lipid content was reduced in ACEA+RIM but not with RIM alone. Collectively, our results support that lipolysis may be reduced by CB1R stimulation in NLNG cows but not in periparturient cows. In addition, our findings demonstrate that adipogenesis and lipogenesis are enhanced by activation of CB1R in the AT of NLNG dairy cows. In summary, we provide initial evidence which supports that the sensitivity of the AT endocannabinoid system to endocannabinoids, and its ability to modulate AT lipolysis, adipogenesis, and lipogenesis, vary based on dairy cows' lactation stage.

Lipopolysaccharide induces lipolysis and insulin resistance in adipose tissue from dairy cows.

Intense and protracted adipose tissue (AT) fat mobilization increases the risk of metabolic and inflammatory periparturient diseases in dairy cows. This vulnerability increases when cows have endotoxemia-common during periparturient diseases such as mastitis, metritis, and pneumonia-but the mechanisms are unknown. Fat mobilization intensity is determined by the balance between lipolysis and lipogenesis. Around parturition, the rate of lipolysis surpasses that of lipogenesis, leading to enhanced free fatty acid release into the circulation. We hypothesized that exposure to endotoxin (ET) increases AT lipolysis by activation of classic and inflammatory lipolytic pathways and reduction of insulin sensitivity. In experiment 1, subcutaneous AT (SCAT) explants were collected from periparturient (n = 12) Holstein cows at 11 ± 3.6 d (mean ± SE) before calving, and 6 ± 1 d and 13 ± 1.4 d after parturition. Explants were treated with the endotoxin lipopolysaccharide (LPS; 20 µg/mL; basal = 0 µg/mL) for 3 h. The effect of LPS on lipolysis was assessed in the presence of the ß-adrenergic agonist and promoter of lipolysis isoproterenol (ISO; 1 µM; LPS+ISO). In experiment 2, SCAT explants were harvested from 24 nonlactating, nongestating multiparous Holstein dairy cows and exposed to the same treatments as in experiment 1 for 3 and 7 h. The effect of LPS on the antilipolytic responses induced by insulin (INS = 1 µL/L, LPS+INS) was established during ISO stimulation [ISO+INS, LPS+ISO+INS]. The characterization of lipolysis included the quantification of glycerol release and the assessment of markers of lipase activity [adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and phosphorylated HSL Ser563 (pHSL)], and insulin pathway activation (AKT, pAKT) using capillary electrophoresis. Inflammatory gene networks were evaluated by real-time quantitative PCR. In periparturient cows, LPS increased AT lipolysis by 67 ± 12% at 3 h across all time points compared with basal. In nonlactating cows, LPS was an effective lipolytic agent at 3 h and 7 h, increasing glycerol release by 115 ± 18% and 68.7 ± 16%, respectively, relative to basal. In experiment 2, LPS enhanced ATGL activity with minimal HSL activation at 3 h. In contrast, at 7 h, LPS increased HSL phosphorylation (i.e., HSL activity) by 123 ± 11%. The LPS-induced HSL lipolytic activity at 7 h coincided with the activation of the MEK/ERK inflammatory pathway. In experiment 2, INS reduced the lipolytic effect of ISO (ISO+INS: -63 ± 18%) and LPS (LPS+INS: -45.2 ± 18%) at 3 h. However, the antilipolytic effect of INS was lost in the presence of LPS at 7 h (LPS+INS: -16.3 ± 16%) and LPS+ISO+INS at 3 and 7 h (-3.84 ± 23.6% and -21.2 ± 14.6%). Accordingly, LPS reduced pAKT:AKT (0.11 ± 0.07) compared with basal (0.18 ± 0.05) at 7 h. Our results indicated that exposure to LPS activated the classic and inflammatory lipolytic pathways and reduced insulin sensitivity in SCAT. These data provide evidence that during endotoxemia, dairy cows may be more susceptible to lipolysis dysregulation and loss of adipocyte sensitivity to the antilipolytic action of insulin.

The politics of vulnerable masculinity in couple therapy.

Couple therapy and related literature has problematized men's emotional inexpressiveness as constraining for men and as contributing to men's privileged and dominating position vis-à-vis women. Fostering men's emotionality in and outside of therapy has been proposed as a way to improve men's well-being and relationships and promote gender equality. Critical masculinity scholars have noted that many men now enact vulnerable ("softer") and emotional forms of masculinity. Yet, there is lack of insight into how such enactment may intersect with gender inequality. This article presents a critical thematic analysis of 30 transcribed videotaped couple therapy sessions focusing on the performance of men's affective masculinities and the political dimensions of men's increasing emotionality within couple therapy. The study shows that vulnerable masculinities, although argued as bearing the potential to foster relational and social change, may also obscure continuing commitment to dominant masculinity norms. Implications for practice are discussed.

A proposed modulatory role of the endocannabinoid system on adipose tissue metabolism and appetite in periparturient dairy cows.

To sustain the nutrient demands of rapid fetal growth, parturition, and milk synthesis, periparturient dairy cows mobilize adipose tissue fatty acid stores through lipolysis. This process induces an inflammatory response within AT that is resolved as lactation progresses; however, excessive and protracted lipolysis compounds the risk for metabolic and inflammatory diseases. The suppression of lipolytic action and inflammation, along with amplification of adipogenesis and lipogenesis, serve as prospective therapeutic targets for improving the health of periparturient dairy cows. Generally, the activation of cannabinoid receptors by endocannabinoids enhances adipogenesis and lipogenesis, suppresses lipolysis, and increases appetite in mammals. These biological effects of activating the endocannabinoid system open the possibility of harnessing the endocannabinoid system through nutritional intervention in dairy herds as a potential tool to improve dairy cows' health, although much is still to be revealed in this context. This review summarizes the current knowledge surrounding the components of the endocannabinoid system, elaborates on the metabolic effects of its activation, and explores the potential to modulate its activity in periparturient dairy cows.